Showing papers on "Catecholamine published in 2013"
TL;DR: By taking advantage of studies using subsecond voltammetric techniques in behaving animals to study how rapid changes in DA levels affect behavior, this review examines the spatial and temporal features of DA release and how it relates to both normal learning and similarities to pathological learning in the form of addiction.
Abstract: The catecholamine dopamine (DA) has been implicated in a host of neural processes as diverse as schizophrenia, parkinsonism and reward encoding. Importantly, these distinct features of DA function are due in large part to separate neural circuits involving connections arising from different DA-releasing nuclei and projections to separate afferent targets. Emerging data has suggested that this same principle of separate neural circuits may be applicable within structural subregions, such as the core and shell of the nucleus accumbens (NAc). Further, DA may act selectively on smaller ensembles of cells (or, microcircuits) via differential DA receptor density and distinct inputs and outputs of the microcircuits, thus enabling new learning about Pavlovian cues, instrumental responses, subjective reward processing and decision-making. In this review, by taking advantage of studies using subsecond voltammetric techniques in behaving animals to study how rapid changes in DA levels affect behavior, we examine the spatial and temporal features of DA release and how it relates to both normal learning and similarities to pathological learning in the form of addiction.
107 citations
TL;DR: Redox balance, which is determined by mutual antagonism between HIF-α isoforms, establishes the set point for hypoxic sensing by the carotid body and adrenal medulla, and is required for maintenance of cardio-respiratory homeostasis.
Abstract: Breathing and blood pressure are under constant homeostatic regulation to maintain optimal oxygen delivery to the tissues. Chemosensory reflexes initiated by the carotid body and catecholamine secretion from the adrenal medulla are the principal mechanisms for maintaining respiratory and cardiovascular homeostasis; however, the underlying molecular mechanisms are not known. Here, we report that balanced activity of hypoxia-inducible factor-1 (HIF-1) and HIF-2 is critical for oxygen sensing by the carotid body and adrenal medulla, and for their control of cardio-respiratory function. In Hif2α+/− mice, partial HIF-2α deficiency increased levels of HIF-1α and NADPH oxidase 2, leading to an oxidized intracellular redox state, exaggerated hypoxic sensitivity, and cardio-respiratory abnormalities, which were reversed by treatment with a HIF-1α inhibitor or a superoxide anion scavenger. Conversely, in Hif1α+/− mice, partial HIF-1α deficiency increased levels of HIF-2α and superoxide dismutase 2, leading to a reduced intracellular redox state, blunted oxygen sensing, and impaired carotid body and ventilatory responses to chronic hypoxia, which were corrected by treatment with a HIF-2α inhibitor. None of the abnormalities observed in Hif1α+/− mice or Hif2α+/− mice were observed in Hif1α+/−;Hif2α+/− mice. These observations demonstrate that redox balance, which is determined by mutual antagonism between HIF-α isoforms, establishes the set point for hypoxic sensing by the carotid body and adrenal medulla, and is required for maintenance of cardio-respiratory homeostasis.
80 citations
TL;DR: It is interesting to note that the effects of age, sex, and degree of obesity and the impact of very intense exercise on the catecholamine response have not yet been well examined, and the hormonal concentrations measured in the majority of obesity studies did not take into account plasma volume changes.
Abstract: Excess body fat in obese individuals can affect the catecholamine response to various stimuli. Indeed, several studies report lower plasma catecholamine concentrations in obese subjects compared with nonobese subjects in response to submaximal or maximal exercise. This low catecholamine response reflects decreased sympathetic nervous system (SNS) activity. Although the relationship between the SNS and obesity is not well established, some authors have suggested that low SNS activity may contribute to the development of obesity. A decreased catecholamine response could affect α- and β-adrenoceptor sensitivity in adipose tissue, reducing lipolysis and increasing fat stores. Few studies have examined the effects of obesity on the plasma catecholamine response at rest and during exercise in adolescents. It is interesting to note that the effects of age, sex, and degree of obesity and the impact of very intense exercise on the catecholamine response have not yet been well examined. Moreover, the hormonal concentrations measured in the majority of obesity studies did not take into account plasma volume changes. This methodological factor can also undoubtedly influence plasma catecholamine results.
67 citations
TL;DR: Stress-induced alteration of the sympathetic nervous system occurs in man as in experimental animals, and hypertension is associated with a loss of slow-wave sleep, when sympathetic nerve activity is lowest.
Abstract: The sympathetic nervous system not only regulates cardiovascular and metabolic responses to stress but also is altered by stress. The sympathoneural and sympathoadrenomedullary systems are modified by different metabolic pathways and have different responses to short- and to long-term stressors. Stress also induces nonneuronal catecholamine enzymes, primarily through corticosteroids. Catecholamine synthetic enzymes are induced by different pathways in response to short- and long-term acting stressors, like cold exposure or immobilization, and differently in the sympathetic ganglia and the adrenal medulla. However, a long-term exposure to one stressor can increase the response to a second, different stressor. Tyrosine hydroxylase gene transcription increases after only 5min of immobilization through phosphorylation of CREB, but this response is short lived. However, repeated stress gives a longer-lived response utilizing transcription factors such as Egr-1 and Fra-2. Glucocorticoids and ACTH also induce sympathoneural enzymes leading to distinct patterns of short-term and long-lived activation of the sympathetic nervous system. Nonneuronal phenylethanolamine N-methyltransferase (PNMT) develops early in the heart and then diminishes. However, intrinsic cardiac adrenergic cells remain and nonneuronal PNMT is present in many cells of the adult organism and increases in response to glucocorticoids. Both stress-induced and administered glucocorticoids induce fetal PNMT and hypertension. Human stressors such as caring for an ill spouse or sleep apnea cause a persistent increase in blood norepinephrine, increased blood pressure, and downregulated catecholamine receptors. Hypertension is associated with a loss of slow-wave sleep, when sympathetic nerve activity is lowest. These findings indicate that stress-induced alteration of the sympathetic nervous system occurs in man as in experimental animals.
66 citations
TL;DR: The present experiments show that CA secretion evoked by direct high-frequency stimulation of the splanchnic nerve is abolished in native adrenal slices from male PACAP-deficient mice, and show that PACAP is the dominant adrenomedullary neurotransmitter during conditions of enhanced secretory demand.
Abstract: The neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a cotransmitter of acetylcholine at the adrenomedullary synapse, where autonomic regulation of hormone secretion occurs We have previously reported that survival of prolonged metabolic stress in mice requires PACAP-dependent biosynthesis and secretion of adrenomedullary catecholamines (CAs) In the present experiments, we show that CA secretion evoked by direct high-frequency stimulation of the splanchnic nerve is abolished in native adrenal slices from male PACAP-deficient mice Further, we demonstrate that PACAP is both necessary and sufficient for CA secretion ex vivo during stimulation protocols designed to mimic stress In vivo, up-regulation of transcripts encoding adrenomedullary CA-synthesizing enzymes (tyrosine hydroxylase, phenylethanolamine N-methyltransferase) in response to both psychogenic and metabolic stressors (restraint and hypoglycemia) is PACAP-dependent Stressor-induced alteration of the adrenomedullary secretory cocktail also appears to require PACAP, because up-regulation of galanin mRNA is abrogated in male PACAP-deficient mice We further show that hypoglycemia-induced corticosterone secretion is not PACAP-dependent, ruling out the possibility that glucocorticoids are the main mediators of the aforementioned effects Instead, experiments with bovine chromaffin cells suggest that PACAP acts directly at the level of the adrenal medulla By integrating prolonged CA secretion, expression of biosynthetic enzymes and production of modulatory neuropeptides such as galanin, PACAP is crucial for adrenomedullary function Importantly, our results show that PACAP is the dominant adrenomedullary neurotransmitter during conditions of enhanced secretory demand
66 citations
TL;DR: The utility of the method was demonstrated by selectively labeling and imaging norepinephrine in secretory vesicles such that discrimination between nore Pinephrine- and epinephrine-enriched populations of chromaffin cells was observed.
Abstract: A method for the selective labeling and imaging of catecholamines in live and fixed secretory cells is reported. The method integrates a tailored approach using a novel fluorescence-based turn-on molecular sensor (NeuroSensor 521) that can exploit the high concentration of neurotransmitters and acidic environment within secretory vesicles for the selective recognition of norepinephrine and dopamine. The utility of the method was demonstrated by selectively labeling and imaging norepinephrine in secretory vesicles such that discrimination between norepinephrine- and epinephrine-enriched populations of chromaffin cells was observed. This method was validated in fixed cells by co-staining with an anti-PNMT antibody.
66 citations
TL;DR: It has been demonstrated that exercise reverses β-AR dysfunction by restoring cardiac receptor membrane density and G-protein-dependent adenylyl cyclase activation and shows a therapeutic effect on age-related impairment of vascular reactivity to adrenergic stimulation.
Abstract: In heart failure (HF), exercise has been shown to modulate cardiac sympathetic hyperactivation which is one of the earliest features of neurohormonal derangement in this syndrome and correlates with adverse outcome. An important molecular alteration related to chronic sympathetic overstimulation in HF is represented by cardiac β-adrenergic receptor (β-AR) dysfunction. It has been demonstrated that exercise reverses β-AR dysfunction by restoring cardiac receptor membrane density and G-protein-dependent adenylyl cyclase activation. In particular, several evidence indicate that exercise reduces levels of cardiac G-protein coupled receptor kinase-2 (GRK2) which is known to be involved in both β1-AR and β2-AR dysregulation in HF. Similar alterations of β-AR system have been described also in the senescent heart. It has also been demonstrated that exercise training restores adrenal GRK2/α-2AR/catecholamine (CA) production axis. At vascular level, exercise shows a therapeutic effect on age-related impairment of vascular reactivity to adrenergic stimulation and restores β-AR-dependent vasodilatation by increasing vascular β-AR responsiveness and reducing endothelial GRK2 activity. Sympathetic nervous system overdrive is thought to account for >50% of all cases of hypertension and a lack of balance between parasympathetic and sympathetic modulation has been observed in hypertensive subjects. Non-pharmacological, lifestyle interventions have been associated with reductions in SNS overactivity and blood pressure in hypertension. Several evidence have highlighted the blood pressure lowering effects of aerobic endurance exercise in patients with hypertension and the significant reduction in sympathetic neural activity has been reported as one of the main mechanisms explaining the favorable effects of exercise on blood pressure control.
65 citations
TL;DR: DA stabilizes tumor blood vessels through activation of pericyte cAMP-protein kinase A signaling pathway by DR1, and could have implications for blocking the stimulatory effects of chronic stress on tumor growth.
64 citations
TL;DR: Data suggest that in CRPS, norepinephrine released from sympathetic nerve terminals stimulates &bgr;2‐ARs expressed on epidermal keratinocytes, resulting in local IL‐6 production, and ultimately, pain sensitization.
Abstract: In many patients, the sympathetic nervous system supports pain and other features of complex regional pain syndrome (CRPS). Accumulating evidence suggests that interleukin (IL)-6 also plays a role in CRPS, and that catecholamines stimulate production of IL-6 in several tissues. We hypothesized that norepinephrine acting through specific adrenergic receptors expressed on keratinocytes stimulates the production of IL-6 and leads to nociceptive sensitization in a rat tibial fracture/cast model of CRPS. Our approach involved catecholamine depletion using 6-hydroxydopamine or, alternatively, guanethidine, to explore sympathetic contributions. Both agents substantially reduced nociceptive sensitization and selectively reduced the production of IL-6 in skin. Antagonism of IL-6 signaling using TB-2-081 also reduced sensitization in this model. Experiments using a rat keratinocyte cell line demonstrated relatively high levels of b2-adrenergic receptor (b2-AR) expression. Stimulation of this receptor greatly enhanced IL-6 expression when compared to the expression of IL-1b, tumor necrosis factor (TNF)-a, or nerve growth factor. Stimulation of the cells also promoted phosphorylation of the mitogen-activated protein kinases P38, extracellular signal-regulated kinase, and c-Jun amino-terminal kinase. Based on these in vitro results, we returned to animal testing and observed that the selective b2-AR antagonist butoxamine reduced nociceptive sensitization in the CRPS model, and that local injection of the selective b2-AR agonist terbutaline resulted in mechanical allodynia and the production of IL-6 in the cells of the skin. No increases in IL-1b, TNF-a, or nerve growth factor levels were seen, however. These data suggest that in CRPS, norepinephrine released from sympathetic nerve terminals stimulates b2-ARs expressed on epidermal keratinocytes, resulting in local IL-6 production, and ultimately, pain sensitization. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
62 citations
TL;DR: Increased levels of TH, DβH and NPY expression in the rat AM, elevated TH in NTS along with increased plasma NE suggest that single OBI exposure results in increased sympathoexcitation, which may involve the elevated AT1 receptor expression and NADPH oxidase levels in the hypothalamus.
50 citations
TL;DR: Not only did l-theanine treatment exhibit a reversal of the cognitive impairments and oxidative damage induced by CRS, but also reversed the abnormal level of corticosterone in the serum as well as the abnormal levels of catecholamines in the brain and the serum.
TL;DR: The data demonstrate that norepinephrine release in the vBNST differs from dopaminerelease in the dlBNST and the NAc in that it signals the absence of reward rather than responding to reward predictive cues.
TL;DR: Monitoring of adrenal catecholamine secretion and splanchnic nerve stimulation in anaesthetised mice using a microsurgical approach argues for a significant contribution of adrenomedullary gap junctions to catechlamine secretion in vivo.
Abstract: Elucidating the mechanisms whereby neuroendocrine tissues coordinate their input and output signals to ensure appropriate hormone secretion is currently a topical issue. In particular, whether a direct communication mediated by gap junctions between neurosecretory cells contributes to hormone release in vivo still remains unknown. Here we address this issue using a microsurgical approach allowing combined monitoring of adrenal catecholamine secretion and splanchnic nerve stimulation in anaesthetised mice. Pharmacological blockade of adrenal gap junctions by the uncoupling agent carbenoxolone reduces nerve stimulation-evoked catecholamine release in control mice and to a larger extent in stressed mice. In parallel, the gap junction-coupled cell network is extended in stressed mice. Altogether, this argues for a significant contribution of adrenomedullary gap junctions to catecholamine secretion in vivo. As such, gap junctional signalling appears to be a substantial component for neuroendocrine function in the adrenal medulla, as it may represent an additional lever regulating hormone release.
TL;DR: The effects of continuous‐flow HeartMate II LVAD on cardiac sympathetic innervations using [123I]metaiodobenzylguanidine ([ 123I]MIBG) nuclear imaging are examined.
Abstract: Aims
Dilated cardiomyopathy (DCM) patients have abundant levels of norepinephrine secondary to failure of the norepinephrine transporter uptake mechanism. Little is known about the effects of an LV assist device (LVAD) on cardiac sympathetic innervations and norepinephrine transporter dysfunction. This study examines the effects of continuous-flow HeartMate II LVAD on cardiac sympathetic innervations using [123I]metaiodobenzylguanidine ([123I]MIBG) nuclear imaging.
Methods and results
After injecting 431 ± 21 MBq of [123I]MIBG, planar scintigraphy was performed at 15 min and 4 h in 14 consecutive non-diabetic non-ischaemic DCM patients. Scans were executed early post-LVAD implantation (T1) and prior to either device explantation for myocardial recovery or transplant listing (T2). [123I]MIBG measured parameters included early and delayed heart–mediastinum (H/M) ratios and washout rate (W/O). Catecholamine levels were measured using liquid chromatography–mass spectrometry. Following 208.4 ± 85.5 days of LVAD support, both early and delayed H/M ratios increased by 42.1% (P < 0.001) and 54.7% (P < 0.001), respectively. The W/O rate decreased by 46% (P = 0.003). Plasma norepinephrine, epinephrine, and dopamine decreased significantly in correlation with [123I]MIBG parameters. Ten patients had recovered and had their device explanted as they had demonstrated a higher percentage change in delayed H/M ratio, W/O rate, and norepinephrine levels. Linear regression analysis revealed a strong correlation between percentage changes in both norepinephrine and epinephrine and myocardial recovery.
Conclusion
Combination therapy with LVAD and drug resulted in enhancement of [123I]MIBG uptake in DCM patients.
TL;DR: The finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis.
Abstract: Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.
TL;DR: Analogy to a bank robber's getaway car conveys the catecholaldehyde hypothesis, according to which buildup of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) causes or contributes to the death of dopamine neurons.
Abstract: This chapter is on biomarkers, mechanisms, and potential treatment of catecholamine neuron loss in Parkinson disease (PD). PD is characterized by a movement disorder from loss of nigrostriatal dopamine neurons. An intense search is going on for biomarkers of the disease process. Theoretically, cerebrospinal fluid (CSF) levels of the deaminated DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), should be superior to other neurochemical indices of loss of central dopamine. CSF DOPAC is low in PD-even in patients with recent onset of Parkinsonism. Cardiac norepinephrine depletion is as severe as the loss of putamen dopamine. PD importantly involves nonmotor manifestations, including anosmia, dementia, REM behavior disorder, and orthostatic hypotension, and all of these nonmotor features are associated with neuroimaging evidence for cardiac sympathetic denervation, which seems to occur independently of the movement disorder and striatal dopaminergic lesion. Analogy to a bank robber's getaway car conveys the catecholaldehyde hypothesis, according to which buildup of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the immediate product of the action of monoamine oxidase on cytosolic dopamine, causes or contributes to the death of dopamine neurons. Decreased vesicular uptake of dopamine and decreased DOPAL detoxification by aldehyde dehydrogenase (ALDH) determine this buildup. Vesicular uptake is also markedly decreased in the heart in PD. Multiple factors influence vesicular uptake and ALDH activity. Evidence is accruing for aging-related induction of positive feedback loops and an autotoxic final common pathway in the death of catecholamine neurons, mediated by metabolites produced continuously in neuronal life. The catecholaldehyde hypothesis also leads to testable experimental therapeutic ideas.
TL;DR: The results of the present study show that cocaine, at environmental concentrations, behaves like an endocrine disruptor changing brain dopamine and plasma catecholamine levels and the activity of pituitary–adrenal/thyroid axes.
Abstract: The aim of the present study was to verify if cocaine, at environmental concentrations, influences the endocrine system of the European eel. Silver eels (a stage of the eel life cycle preparing the fish for the oceanic reproductive migration) were exposed to a nominal cocaine concentration of 20 ng/l during 30 days; at the same time, control, carrier, and postexposure recovery groups were made. The effects of cocaine were observed in (1) brain dopamine content, (2) plasma catecholamine levels (dopamine, norepinephrine, and epinephrine), (3) pituitary–adrenal axis activity [plasma adrenocorticotropic hormone (ACTH), corticosterone, cortisol, and aldosterone levels], and (4) pituitary–thyroid axis activity [plasma thyroid-stimulating hormone (TSH), triiodothyronine, and thyroxine levels]. In the treated group, brain dopamine, plasma catecholamines, cortisol, and TSH levels were higher, whereas ACTH, corticosterone, and triiodothyronine levels were lower than controls. In the postexposure recovery group, brain dopamine, plasma dopamine and epinephrine, and thyroxine levels further increased, whereas plasma norepinephrine, cortisol, and corticosterone levels were similar to treated values. Finally, ACTH and TSH were similar, whereas triiodothyronine levels were lower than controls. Aldosterone levels were unaffected by cocaine exposure. The results of the present study show that cocaine, at environmental concentrations, behaves like an endocrine disruptor changing brain dopamine and plasma catecholamine levels and the activity of pituitary–adrenal/thyroid axes. Since the endocrine system plays a key role in the metabolic and reproductive processes of the eel, our results suggest that environmental cocaine could be considered another cause for the decline in the European eel.
TL;DR: Catecholamine mobilization during heat shock in rainbow trout probably was not triggered by impaired blood O(2) transport, and this effect of high temperature activating the sympathetic nervous system via a thermosensitive transient receptor potential channel is likely to have been triggered.
Abstract: Rainbow trout (Oncorhynchus mykiss) exposed to an acute heat shock (1 h at 25 °C after raising water temperature from 13 °C to 25 °C over 4 h) mount a significant catecholamine response. The present study investigated the proximate mechanisms underlying catecholamine mobilization. Trout exposed to heat shock in vivo exhibited a significant reduction in arterial O(2) tension, but arterial O(2) concentration was not affected by heat shock, nor was catecholamine release during heat shock prevented by prior and concomitant exposure to hyperoxia (to prevent the fall in arterial O(2) tension). Thus, catecholamine mobilization probably was not triggered by impaired blood O(2) transport. Heat-shocked trout also exhibited an elevation of arterial CO(2) tension coupled with a fall in arterial pH, but these factors are not expected to trigger catecholamine release. The changes in blood O(2) and CO(2) tension occurred despite a significant hyperventilatory response to heat shock. Future studies should investigate whether catecholamine mobilization during heat shock in rainbow trout is triggered by a specific effect of high temperature activating the sympathetic nervous system via a thermosensitive transient receptor potential channel.
TL;DR: Testing whether sympathetic activity shows an association with a tonic dimension of decision-making, exploratory tendency represented by entropy in information theory, and further examined the neural mechanisms of the association shed new light about a role of bodily states in decision- making and underlying neural mechanisms.
TL;DR: The sympathetic limb of the stress response exhibits an activity-dependent form of long-lasting plasticity, which indicates that acute stress leads to a lasting increase in secretory capacity in vivo but does not alter sympathetic tone, which appears to be an adaptive response.
Abstract: Acute stress evokes the fight-or-flight reflex, which via release of the catecholamine hormones affects the function of every major organ. Although the reflex is transient, it has lasting consequences that produce an exaggerated response when stress is reexperienced. How this change is encoded is not known. We investigated whether the reflex affects the adrenal component of the sympathetic nervous system, a major branch of the stress response. Mice were briefly exposed to the cold-water forced swim test (FST) which evoked an increase in circulating catecholamines. Although this hormonal response was transient, the FST led to a long-lasting increase in the catecholamine secretory capacity measured amperometrically from chromaffin cells and in the expression of tyrosine hydroxylase. A variety of approaches indicate that these changes are regulated postsynaptically by neuropeptide Y (NPY), an adrenal cotransmitter. Using immunohistochemistry, RT-PCR, and NPY(GFP) BAC mice, we find that NPY is synthesized by all chromaffin cells. Stress failed to increase secretory capacity in NPY knock-out mice. Genetic or pharmacological interference with NPY and Y1 (but not Y2 or Y5) receptor signaling attenuated the stress-induced change in tyrosine hydroxylase expression. These results indicate that, under basal conditions, adrenal signaling is tonically inhibited by NPY, but stress overrides this autocrine negative feedback loop. Because acute stress leads to a lasting increase in secretory capacity in vivo but does not alter sympathetic tone, these postsynaptic changes appear to be an adaptive response. We conclude that the sympathetic limb of the stress response exhibits an activity-dependent form of long-lasting plasticity.
TL;DR: Catecholamine release was evoked by both the hypothalamic–pituitary–adrenal axis and autocrine signaling by BDNF in the adrenal gland and BDNF–TrkB interaction may play a role in a positive feedback loop in the Adrenal medulla during immobilization stress.
Abstract: Expression of tyrosine receptor kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), is markedly elevated in the adrenal medulla during immobilization stress. Catecholamine release was confirmed in vitro by stimulating chromaffin cells with recombinant BDNF. We investigated the role of TrkB and the localization of BDNF in the adrenal gland during immobilization stress for 60 min. Blood catecholamine levels increased after stimulation with TrkB expressed in the adrenal medulla during 60-min stress; however, blood catecholamine levels did not increase in adrenalectomized rats. Furthermore, expression of BDNF mRNA and protein was detected in the adrenal medulla during 60-min stress. Similarly, in rats undergoing sympathetic nerve block with propranolol, BDNF mRNA and protein were detected in the adrenal medulla during 60-min stress. These results suggest that signal transduction of TrkB in the adrenal medulla evokes catecholamine release. In addition, catecholamine release was evoked by both the hypothalamic–pituitary–adrenal axis and autocrine signaling by BDNF in the adrenal gland. BDNF–TrkB interaction may play a role in a positive feedback loop in the adrenal medulla during immobilization stress.
TL;DR: Elevated systemic PG levels can directly suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of the effects of endogenously-released PGs.
Abstract: Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and prostaglandin (PG)-mediated responses. However, PGs are synthesized locally following tissue damage, driving proinflammatory and CORT responses, while their systemic levels are often unaffected. Thus, we herein studied the role of adrenal factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and sham-operated F344 rats subjected to surgery or PGE 2 administration. In vivo and ex vivo approaches were employed, based on intravenous administration of the NK-sensitive MADB106 tumor line, and based on ex vivo assessment of YAC-1 and MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics of the impact of epinephrine, CORT, and PGE 2 on NKCC. The results indicated that suppression of NKCC by epinephrine and PGE 2 are short lasting, and cannot be evident when these compounds are removed from the in vitro assay milieu, or in the context of ex vivo assessment of NKCC. In contrast, the effects of CORT are long-lasting and are reflected in both conditions even after its removal. Marginating-pulmonary NKCC was less susceptible to suppression than circulating NKCC, when tested against the xenogeneic YAC-1 target line, but not against the syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms. Overall, these findings indicate that elevated systemic PG levels can directly suppress NKCC in vivo , but following laparotomy adrenal hormones mediate most of the effects of endogenously-released PGs. Additionally, the ex vivo approach seems limited in reflecting the short-lasting NK-suppressive effects of catecholamines and PGs.
TL;DR: Catecholamines, which are physiologically important neurotransmitters and hormones, apparently decrease in the brain and plasma as some species age, are investigated using mice to investigate whether age‐related changes occur in adrenal catecholamine levels and in the expression of catechlamine synthetic enzymes.
Abstract: Aim: Catecholamines, which are physiologically important neurotransmitters and hormones, apparently decrease in the brain and plasma as some species age. Because this observation has engendered controversy, we used mice to investigate whether age-related changes occur in adrenal catecholamine levels and in the expression of catecholamine synthetic enzymes.
Methods: Adrenal glands were collected from male C57BL/6NCr mice at the ages of 6, 12 and 24 months. Catecholamines, such as dopamine (DA), noradrenaline (NA) and adrenaline (AD) from those glands, were measured by using a highly sensitive liquid chromatographic method with peroxyoxalate chemiluminescence reaction detection. Tyrosine hydroxylase (TH), dopa decarboxylase, dopamine beta hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression levels were measured by quantitative real-time polymerase chain reaction.
Results: Although DA levels in the adrenals of 24-month-old mice were higher than in 6- and 12-month-old mice, the AD content decreased with age. In such mice, the ratio of DA to NA at 24 months was lower than at 12 months, and the ratio of NA to AD content at 24 months was significantly lower than at 6 months. The mRNA expression ratios in TH, DBH and PNMT in 24-month-old mice were all lower than in 12-month-old mice.
Conclusions: These results strongly suggest that catecholamine synthesis, in general, declines with aging in the adrenal glands of mice and that AD, in particular, undergoes a significant decrease with advancing age. Geriatr Gerontol Int 2013; 13: 490–496.
TL;DR: Tyrosine supplementation increases the catecholamine level and reduces the impairment of cognitive performance during HE, and plasma norepinephrine, dopamine and epinephrine levels were detected in tyrosine supplemented group post heat exposure.
TL;DR: Results showed that repeated ECS enhance DA activity in the SNc and NE transmission in the FMN, which could be a part of the mechanism behind the alleviation of depressive symptoms, including motor retardation, by ECT.
Abstract: Electroconvulsive therapy (ECT) treats depression by repeated administration of seizure-inducing electrical stimuli. To assess the effects of repeated electroconvulsive shocks (ECSs), an animal model of ECT on monoamine transmission, Sprague-Dawley rats were administered 6 ECS over 2 weeks and in vivo single-unit extracellular electrophysiological recordings were obtained 48 h after the final ECS. Overall firing activity of dopamine (DA) neurons in the ventral tegmental area was unchanged following repeated ECS. In the locus coeruleus (LC), the burst activity of norepinephrine (NE) neurons was increased while population activity was decreased after ECS. In the substantia nigra pars compacta (SNc), there were more spontaneously active neurons, suggesting greater DA tone in the nigrostriatal motor pathway, which may contribute to an alleviation of motor retardation. In the facial motor nucleus (FMN), facilitation of electrophysiological activity by serotonin (5-HT), and NE was determined to be through the 5-HT2C receptor and α1 -adrenoceptor, respectively. Locally administered NE, but not 5-HT, facilitated glutamate-induced firing following repeated ECS, which may contribute to improved motor function. These results showed that repeated ECS enhance DA activity in the SNc and NE transmission in the FMN, which could be a part of the mechanism behind the alleviation of depressive symptoms, including motor retardation, by ECT.
TL;DR: In rat macrophages, adrenalectomy increased tyrosine hydroxylase expression, decreased monoamine oxidase‐A mRNA expression and augmented β2‐adrenoceptor expression, however, notwithstanding these changes, propranolol treatment increased lipopolysaccharide‐stimulated tumour necrosis factor‐α production in macrophage from adrenalectomized and non‐operated rats to a similar extent.
Abstract: Catecholamines modulate the production of inflammatory mediators by macrophages in an autocrine/paracrine manner. They also tune β2-adrenoceptor expression. Glucocorticoids influence catecholamine metabolism and adrenoceptor expression in many cell types. We hypothesized that adrenal hormones affect the production of tumour necrosis factor-α (TNF-α) and NO by macrophages by altering the modulatory influence of catecholamines. To prove the hypothesis, peritoneal exudate macrophages from propranolol-treated non-operated and adrenalectomized rats and from corticosterone-supplemented adrenalectomized rats were examined for lipopolysaccharide-stimulated NO and TNF-α production in vitro and for expression of β2-adrenoceptors and major catecholamine-metabolizing enzymes. Glucocorticoid deprivation increased NO production by macrophages, whereas 4 days of propranolol treatment was ineffective in this respect. However, propranolol treatment, via β2-adrenoceptor blockade, increased production of TNF-α by macrophages in both non-operated and adrenalectomized rats (showing dramatically enhanced TNF-α production due to a lack of circulating glucocorticoids) for the same value. The expression of β2-adrenoceptor was increased in peritoneal macrophages that were freshly isolated from non-operated, propranolol-treated and adrenalectomized rats (due to adrenal catecholamine deficiency). Propranolol did not affect macrophage β2-adrenoceptor expression in adrenalectomized rats. Given that propranolol increased the density of macrophage tyrosine hydroxylase expression only in non-operated rats and affected the mRNA expression of monoamine oxidase-A in neither non-operated nor adrenalectomized animals, a significant influence of propranolol on peritoneal exudate cell noradrenaline content was found only in non-operated rats. A lack of circulating adrenal hormones also affected noradrenaline metabolism and content in peritoneal exudate cells including macrophages. Collectively, despite differences in the abundance of macrophage catecholamine-β2-adrenoceptor system components and in the TNF-α response to lipopolysaccharide between adrenalectomized and non-operated rats, propranolol increased TNF-α production by the same amount in macrophages from these two groups of animals.
TL;DR: Neonatal overfeeding led to higher adrenomedullary function, but the liver β2-adrenergic receptor content was reduced, which may contribute to the hepatic dysfunction characteristic of liver obesity complications.
Abstract: Rats that are overfed during lactation exhibit neonatal hyperleptinemia and higher visceral adiposity, hypertension, higher liver oxidative stress and insulin resistance in the liver as adults. Previously, we demonstrated that neonatal hyperleptinemia is associated with adrenal medullary hyperfunction, hypertension and liver steatosis in adulthood. Therefore, we hypothesised that adrenal and liver functions are altered in adult obese rats that were overfed during lactation, which would underlie their hypertension and liver alterations. The litter size was reduced from ten to three male pups on the third day of lactation until weaning (SL) to induce early overfeeding in Wistar rats. The control group had ten rats per litter (NL). Rats had free access to standard diet, and water after weaning until the rats were 180 days old. The SL group exhibited higher adrenal catecholamine content (absolute: +35% and relative: +40%), tyrosine hydroxylase (+31%) and DOPA decarboxylase (+90%) protein contents and basal catecholamine secretion in vitro (+57%). However, the hormones of the hypothalamic-pituitary-adrenal cortex axis were unchanged. β3-adrenergic receptor content in visceral adipose tissue was unchanged in SL rats, but the β2-adrenergic receptor content in the liver was lower in this group (−45%). The SL group exhibited higher glycogen and triglycerides contents in the liver (+79 and +49%, respectively), which suggested microesteatosis. Neonatal overfeeding led to higher adrenomedullary function, but the liver β2-adrenergic receptor content was reduced. These results may contribute to the hepatic dysfunction characteristic of liver obesity complications.
TL;DR: It is shown that CAT production occurs in adipose tissue and may be activated by stress directly in adipocytes, and potential physiological importance of these findings is accentuated by parallel increase in expression of vesicular monoamine transporter 1, indicating a need for CAT storage in adipocyte vesicles.
Abstract: Catecholamines (CATs), the major regulator of lipolysis in adipose tissue, are produced mainly by the sympathoadrenal system. However, recent studies report endogenous CAT production in adipocytes themselves. This study investigated the effects of single and repeated (7–14 times) immobilization (IMO) stress on CAT production in various fat depots of the rat. Single IMO quickly induced a rise of norepinephrine (NE) and epinephrine (EPI) concentration in mesenteric and brown adipose depots. Adaptive response to repeated IMO included robust increases of NE and EPI levels in mesenteric and subcutaneous adipose tissue. These changes likely reflect the activation of sympathetic nervous system in fat depots by IMO. However, this process was also paralleled by an increase in tyrosine hydroxylase gene expression in mesenteric fat, suggesting regulation of endogenous CAT production in adipose tissue cells. Detailed time-course analysis (time course 10, 30, and 120 min) clearly showed that repeated stress led to inc...
TL;DR: The results indicate that presynaptic α2-adrenoceptor regulation of norepinephrine release from nerve vesicles and epinephrine secretion is dysfunctional in SHRs, but can be restored by clonidine, and tyramine-infusion does allow presynptic regulation of vesicular release to be accurately assessed by measuring differences in plasma nore Pinephrine concentration.
Abstract: α2-adrenoceptor-activation lowers central sympathetic output, peripheral, vesicular norepinephrine release, epinephrine secretion and modulates vascular tension. We previously demonstrated that α2-adrenoceptor-mediated inhibition of basal norepinephrine release was not reflected in plasma unless re-uptake through the norepinephrine transporter (NET) was blocked. Tyramine activates reverse norepinephrine transport through NET. Here we tested the hypothesis that tyramine, by engaging NET in release, also blocks re-uptake and therefore allows manipulation of pre-junctional α2-adrenoceptors to directly regulate norepinephrine overflow to plasma. We compared in anaesthetised spontaneously hypertensive rats (SHRs) and normotensive controls (WKYs), the effect of α2-adrenoreceptor antagonist (L-659,066) and/or agonist (clonidine) on norepinephrine overflow and increase in total peripheral vascular resistance (TPR) evoked by tyramine infusion (1.26 μmol/min/kg, 15 min) and epinephrine secretion activated by the surgical stress. TPR was computed as cardiac output, recorded as ascending aortic flow, divided by blood pressure. Plasma catecholamine concentrations after tyramine were higher in SHRs than WKYs. Pre-treatment with L-659,066 increased the catecholamine concentrations in WKYs, but only if combined with clonidine in SHRs. Clonidine alone reduced tyramine-induced norepinephrine overflow in SHRs, and epinephrine in both strains. Tyramine-induced increase in TPR was not different after clonidine, eliminated after L-659,066 and L-659,066+clonidine in WKYs, but only after L-659,066+clonidine in SHRs. We conclude that tyramine infusion does allow presynaptic regulation of vesicular release to be accurately assessed by measuring differences in plasma norepinephrine concentration. Our results indicate that pre-synaptic α2-adrenoceptor regulation of norepinephrine release from nerve vesicles and epinephrine secretion is dysfunctional in SHRs, but can be restored by clonidine.
TL;DR: It is suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors.