Showing papers on "Catecholamine published in 1988"

Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover.

Abstract: SINCE the sympathetic nervous system has such a central place in homeostasis in general, and in circulatory adaptation in particular, it is paradoxical that so little is known about the possible contribution of disturbed sympathetic nervous function to the development of human diseases. Clinical tests of sympathetic nervous system activity have, by and large, been routinely applied in one setting only: the detection of sympathetic nervous failure, from autonomic insufficiency syndromes, in patients with postural hypotension. A list of \"candidate\" diseases for sympathetic nervous system dysfunction might include, for example, essential hypertension, cardiac failure, coronary artery spasm, cirrhosis, mitral valve prolapse, and Raynaud's syndrome. Until very recently, the picture of sympathetic nervous pathophysiology for conditions such as these was particularly sketchy, mainly because of the rudimentary nature of the tests of sympathetic nervous system function available to investigative clinical medicine. Pertinent questions have gone incompletely answered at best — questions such as: Is the sympathetic nervous system directly involved in the early pathogenesis of essential hypertension? Is increased renal sympathetic activity a common cause of sodium retention in edematous states? Is increased cardiac sympathetic nerve firing an important element in the development of cardiac arrhythmias in humans?

Catecholamine toxicity in cerebral cortex in dissociated cell culture.

Abstract: Identification of endogenous toxins and characterization of the mechanisms by which toxins produce cell injury and death may help understand both normal modeling of cell populations and connections in the CNS as well as abnormal cell loss The toxicity of catecholamines intrinsic to the CNS was investigated using the model system of rat cerebral cortex in dissociated cell culture All catecholamines tested, including norepinephrine (NE), dopamine, and epinephrine, were toxic to neurons as well as glia at a concentration of 25 microM when added to cultures 24 hr after plating Toxicity was evident after 48 hr exposure to NE, as monitored by loss of cells from the cultures Toxicity did not seem to be mediated by adrenergic receptors because, although the beta-adrenergic agonist isoproterenol (but not the alpha-adrenergic agonist phenylephrine) was similar in its toxic effect to NE, the beta- adrenergic antagonist atenolol did not block the toxic effect of NE Toxicity could be mimicked by hydrogen peroxide, a product of the oxidative degradation of catecholamines Toxicity of NE was blocked by catalase The neurotoxin 6-hydroxydopamine (6-OHDA), supposedly selective for catecholaminergic neurons, was found to be toxic over the same concentration range as NE These results suggest that endogenous catecholamines may play a role in normal and abnormal cell death, and suggest that caution be used in relying on the specificity of 6-OHDA and other supposedly selective neurotoxins

Stress-related activation of cerebral dopaminergic systems.

Abstract: The changes in dopamine catabolites in various regions of mouse brain have been studied following a variety of behavioral treatments. In confirmation of the results of many others, we find that treatments such as footshock or restraint result in a pronounced activation of dopaminergic systems in the prefrontal cortex, as determined by increases in the content of DOPAC (3,4-dihydroxyphenylacetic acid). However, we also find small but statistically significant increases of DOPAC in the hypothalamus and brain stem even with mild treatments. With restraint and more intense footshock we observe increases of DOPAC in all regions studied, including nucleus accumbens, olfactory tubercle, amygdala, and the striatum. Thus in contrast to previous reports, we find that the DA response in stress is global like that of norepinephrine [as determined by increases of 3-methoxy,4-hydroxyphenylethyleneglycol, (MHPG)], and not specific to the prefrontal cortex. The activation of prefrontal cortex DA metabolism is associated with an activation of the synthetic enzyme tyrosine hydroxylase. The response pattern of catecholamine metabolites is similar following a variety of stressors, including conditioned footshock, training with one footshock in passive avoidance behavior, performance of passive avoidance behavior, and even following exposure to an apparatus in which mice have been shocked previously. Injection of mice with Newcastle disease virus increases plasma corticosterone, and DOPAC and MHPG in the hypothalamus and brain stem, but not the prefrontal cortex. Thus a virus infection can be considered a stressor. Furthermore, intracerebroventricular (ICV) injection of corticotropin-releasing factor (CRF) produces stresslike increases in DOPAC and MHPG concentrations, suggesting that the release of CRF in the brain during stress may mediate the changes in catecholamine metabolism.

Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro.

Abstract: To further our understanding ofthe functional role of catecholaminergic systems in regulating hypothalamic corticotropinreleasing hormone (CRH) secretion, we assessed the direct effects of a multiplicity of catecholamine agonists and antagonists on hypothalamic CRH secretion. To accomplish this, we used an in vitro rat hypothalamic organ culture system in which CRH secretion from single explants was evaluated by a specific RIA (IR-rCRH). Norepinephrine (NE) stimulated IRrCRH secretion dose dependently, with peak effects in the nanomolar range. The effect of NE was antagonized by the mixed a antagonist phentolamine, the a, antagonist prazosin, and the a2 antagonist yohimbine, but not by the ,B blocker, L-propanolol. Compatible with these data were the findings that the a, agonist phenylephrine and the a2 agonist clonidine both stimulated IR-rCRH secretion in a dose-dependent fashion. On the other hand, whereas the fi agonist, isoproterenol, caused a weak, non-dose-dependent increase in IR-rCRH secretion, this effect could not be antagonized by L-propanolol. Despite pretreatment with serotonin and acetylcholine antagonists, the effect ofNE upon IR-rCRH secretion was undiminished, suggesting that NE-induced CRH secretion is not mediated by either neurotransmitter. On the other hand, pretreatment with y-aminobutyric acid (GABA) attenuated NE-induced IR-rCRH secretion. Whereas epinephrine (E) stimulated IR-rCRH secretion, this occurred only at higher concentrations, and was antagonized by phentolamine, but not by L-propanolol. Dopamine (DA) had a weak stimulatory effect that could be antagonized by the DA, receptor antagonist,

In vivo measurement of neuronal uptake of norepinephrine in the human heart.

Abstract: Neuronal uptake (Uptake-1) of the sympathetic neurotransmitter norepinephrine from the circulation in the human heart was assessed in vivo with three techniques. 1) Cardiac removal of intravenously infused tracer-labeled norepinephrine was measured before and after Uptake-1 blockade with desipramine; 2) the difference between the fractional extraction of radioactive norepinephrine and of radioactive isoproterenol, which is not a substrate for neuronal uptake, was used to estimate the removal of norepinephrine by Uptake-1 in the heart compared with other vascular beds (arm, leg, brain, and lungs); and 3) regional arteriovenous differences in radioactive and endogenous dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, were compared in these beds. In untreated patients, cardiac removal of radioactive norepinephrine averaged 79%, whereas in desipramine-treated patients, cardiac removal of radioactive norepinephrine averaged 19%, a value similar to that of isoproterenol in untreated patients (14%), confirming that in the heart the non-neuronal removals of isoproterenol and norepinephrine were similar. In the heart, 69% of delivered norepinephrine was estimated to be removed by Uptake-1, a much higher percentage than that in the arm (14%), leg (7%), brain (10%), and lungs (4%). The cardiac arteriovenous increment in endogenous DHPG (137%) far exceeded that of the other beds (49%, 26%, 39%, and -19%, respectively), and radioactive DHPG in the great cardiac vein exceeded arterial levels by 113%, whereas in the other beds, arterial radioactive DHPG exceeded venous levels. The results indicate that the human heart is exceptionally dependent on neuronal uptake for in vivo removal of circulating norepinephrine.

Stress-related changes in cerebral catecholamine and indoleamine metabolism: lack of effect of adrenalectomy and corticosterone.

Abstract: The concentrations of catecholamine and indoleamine metabolites were measured in intact and adrenalectomized mice to determine whether adrenal hormones mediate or modulate the stress-induced responses. Thirty minutes of footshock resulted in significant increases of the ratios of the dopamine (DA) catabolite, dihydroxyphenylacetic acid (DOPAC), to DA in prefrontal cortex, nucleus accumbens, striatum, hypothalamus, and brainstem, and of homovanillic (HVA)/DA ratios in nucleus accumbens, striatum, amygdala, and hypothalamus. Ratios of 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine (NE) were also increased in prefrontal cortex, nucleus accumbens, septum, amygdala, hypothalamus, hippocampus, and brainstem. The concentration of NE was decreased in amygdala. 5-Hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT, serotonin) ratios and free tryptophan were also increased in every brain region. Very similar data were obtained from mice restrained for 30 min. Adrenalectomy resulted in increased HVA/DA ratios in prefrontal cortex and striatum, and 5-HIAA/5-HT in septum. The stress-related changes were largely similar in adrenalectomized mice. Significant interactions between adrenalectomy and footshock treatment occurred in prefrontal cortical DOPAC/DA and hypothalamic NE which was depleted only in adrenalectomized mice, suggesting tendencies for these measures to be more responsive in adrenalectomized mice. Corticosterone administration (0.5-2.0 mg/kg s.c.) which resulted in plasma concentrations in the physiological range did not alter the concentrations of the cerebral metabolites measured in any region. We conclude that adrenal hormones do not mediate cerebral catecholamine or indoleamine metabolism in stress, although adrenalectomy may affect HVA and 5-HIAA metabolism, and there was a tendency for catecholamines to be more sensitive to stress in adrenalectomized animals.

Adrenomedullary catecholamine release in the fetus and newborn: secretory mechanisms and their role in stress and survival.

Abstract: Catecholamines released by the adrenal medulla during birth play a key role in the adaptation of the newborn to extrauterine life Respiratory, metabolic and cardiovascular adaptations to the hypoxia and other stresses associated with delivery are dependent upon a profound surge of adrenomedullary activity which occurs despite the immaturity of connections between the central nervous system and the adrenal The "non-neurogenic" response seen in the fetus and neonate is thus essential to survival, and any interference either with catecholamine release or with catecholamine actions at adrenergic targets results in loss of the ability to survive hypoxia or other stressors The immature secretory mechanism disappears as a result of development of neural connections, and factors which accelerate ontogeny of neural competence thus lead to premature loss of non-neurogenic secretory capabilities and a consequent increase in vulnerability The fetus and neonate also have unusual proportions of adrenergic receptor subtypes in many tissues; these confer reactivity to specific stimuli associated with birth and with periods in which tissue differentiation may be under adrenergic control Again, the ontogenetic switchover of receptor-mediated mechanisms appears to be a function of the development of neuronal competence, but in this case an important role may be played by a secondary surge in sympathetic tone occurring during the postnatal period Through specialized mechanisms mediating catecholamine secretion and adrenergic responses, the adrenal medulla thus appears to provide both physiological and trophic signals to the fetus and neonate

Prenatal exposure to nicotine via maternal infusions: effects on development of catecholamine systems.

Abstract: The effects of a continuous 16-day gestational exposure to nicotine on development of central and peripheral catecholaminergic pathways were examined in the offspring of dams who received a minipump implant on the 4th day of gestation. Prenatal nicotine exposure resulted in a selective suppression of maturational increases in norepinephrine and dopamine levels and utilization rates in the cerebral cortex and also reduced transmitter levels in sympathetic pathways to the lung and kidney. The regional selectivity of the effect, combined with measurements of synaptosomal uptake of [3H]norepinephrine and of tyrosine hydroxylase activity, all suggested that the alterations in transmitter disposition reflected reduced neural activity as opposed to actions on general cellular development or synaptogenesis. Although the lag in development was largely made up by weaning, deficits in norepinephrine utilization reappeared in young adulthood in the cerebral cortex and midbrain + brainstem, suggesting that lasting functional alterations may occur as a consequence of prenatal nicotine exposure. Comparisons with the results obtained with maternal nicotine injections (which produce largely stimulatory effects on norepinephrine levels and turnover) suggest that the hypoxia/ischemia associated with injected nicotine causes a reactive hyperinnervation; the adverse actions of nicotine on neurotransmitter development are thus highly dependent upon the route of drug administration.

Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats

Abstract: Capsaicin enhances adrenal medullary catecholamine secretion. The participation of the central nervous system on this enhancement by capsaicin was investigated in alpha-chloralose-urethan- or halothane-anesthetized rats. Intravenous administration of capsaicin caused a rapid and marked increase in adrenal sympathetic nerve activity. The nerve activity began to show an increase with the administration of capsaicin at a dosage of 20 micrograms/kg and significantly increased with a dosage of 200 micrograms/kg, i.e., capsaicin was found to cause a dose-dependent increase in adrenal nerve activity. Cholinergic blocking with hexamethonium bromide and atropine sulfate (1 and 5 mg/kg iv, respectively) attenuated the adrenal epinephrine secretion caused by capsaicin. The direct action of capsaicin on adrenal catecholamine secretion was examined using a retrograde perfusion system of left adrenal gland. Up to 8.2 X 10(-5) M capsaicin did not enhance catecholamine secretion from the adrenal gland. These results suggest that the enhancement of physiological catecholamine secretion by capsaicin is mainly through activation of the central nervous system.

Epinephrine potentiates human platelet activation but is not an aggregating agent

Abstract: Epinephrine can in certain in vitro conditions induce the aggregation of human platelets and could play an important role in vivo in the appearance of thrombotic disorders when catecholamine levels are increased. This study examines some functional and biochemical responses to epinephrine. Epinephrine induces the aggregation and serotonin secretion of human platelets in citrated plasma. This is not due to a direct effect of citrate itself, such as the lowering of plasma free Ca2+ but more likely to the generation of traces of thrombin during blood collection, as suggested by abrogation of these platelet responses when hirudin was added before citrate. When washed human platelets suspended in Tyrode buffer containing 2 mM Ca2+, 0.35% albumin and apyrase, and 0.1-100 microM epinephrine were used, no shape change, aggregation, or secretion of serotonin was observed, nor was the platelet ultrastructure modified. Epinephrine does not modify platelet membrane fluidity, as studied with the lipophilic fluorescent probe trimethylammonium-diphenylhexatriene. It has no direct effect on fibrinogen binding to intact platelets, intracellular Ca2+ levels measured by quin2, or protein phosphorylation. Epinephrine potentiates the action of all types of aggregating agents on aggregation, secretion, intracellular Ca2+ levels, membrane fluidity, fibrinogen binding, or protein phosphorylation. These effects are mediated by alpha 2-adrenergic agonists and inhibited by alpha 2-adrenergic antagonists. This study shows that epinephrine alone does not induce modifications of morphology, metabolism, or function of intact and functional washed human platelets and that it cannot be considered per se as an aggregating agent. However, epinephrine interacts with alpha 2-adrenergic receptors on human platelets and potentiates biochemical and aggregatory responses induced by other platelet agonists.

Increase in extracellular dopamine in the striatum during cerebral ischemia: a study utilizing cerebral microdialysis.

Abstract: Unilateral ligation of the left common carotid artery in anesthetized Mongolian gerbils resulted in a steep rise in extracellular dopamine in the ipsilateral striatum in 9 out of 19 animals. Extracellular dopamine was measured by cerebral dialysis in vivo and reached a peak of 0.19 mM at 40 min. At the same time, the level of homovanillic acid fell, whereas the levels of ascorbate and 3,4-dihydroxyphenylacetic acid remained relatively constant. In a separate group of animals studied with a combined dialysis/electrochemistry probe, a rise in the in vivo chronoamperometric signal in three out of six animals correlated with a rise in extracellular dopamine. The number of animals responding in these experiments (roughly 50%) corresponds to the frequency of incompetent Circle of Willis, as well as literature reports of the frequency of signs of stroke in unanesthetized gerbils. These results show a remarkable accumulation of dopamine in extracellular fluid in response to cerebral ischemia. Released dopamine appears to be responsible for the elevated in vivo electrochemical signal previously reported.

Plasma and urinary catecholamines in salt-sensitive idiopathic hypertension.

Abstract: Nineteen patients with normal renin idiopathic hypertension were arbitrarily classified as salt-sensitive or salt-resistant depending on whether their mean arterial pressure did or did not increase by 8% or more when sodium intake was increased. The responses of the two subsets and of five normal subjects to sodium intakes of 9, 109, and 249 mEq/day given for 7 days were as follows: The salt-sensitive subjects retained more sodium than normal and plasma or urinary norepinephrine did not decrease when they were given a high sodium intake; urinary dopamine was normal but did not increase normally when sodium intake was increased. The salt-resistant subjects excreted sodium normally and plasma and urinary norepinephrine was decreased by 30 and 37%, respectively, when they were given a high sodium intake; urinary dopamine was supernormal and did not increase further when sodium intake was increased. Cumulative sodium retention during the high sodium intake was directly related to the percentage of change in plasma norepinephrine in the hypertensive subjects, suggesting that renal adrenergic activity was a factor in the impaired sodium excretion in the salt-sensitive patients. Cumulative sodium retention and the percentage of change in plasma norepinephrine were inversely related to urinary dopamine in the hypertensive subjects, suggesting that increased formation of dopamine in renal and neural tissue in the salt-resistant subjects may have been responsible for the differences between the subsets in renal and adrenergic responses to a high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

CRF activates autonomic nervous system and reduces natural killer cytotoxicity

Abstract: Corticotropin-releasing factor (CRF) acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to those observed after stress. A reduction of immune function has also been described following central administration of CRF. In this study, we examined whether autonomic nervous system activation plays a role in CRF-induced suppression of natural killer (NK) cytotoxicity. synthetic rat CRF (1.0 microgram) microinjected into the lateral ventricle significantly increased plasma concentrations of norepinephrine and reduced splenic NK cell activity in the rat. Pretreatment of the animals with the ganglionic-blocking agent chlorisondamine completely abolished the CRF-induced increase in plasma norepinephrine levels and reduction in NK activity. However, CRF-induced elevations in plasma levels of adrenocorticotropic hormone and corticosterone were not affected by chlorisondamine. The results of this study suggest that activation of the sympathetic nervous system plays a role in CRF-induced suppression of NK cytotoxicity.

Neuronal sodium homoeostatis and axoplasmic amine concentration determine calcium-independent noradrenaline release in normoxic and ischemic rat heart.

Abstract: Calcium-independent noradrenaline release was studied in the isolated perfused rat heart under conditions of normoxia, cyanide intoxication, and ischemia. The release of endogenous noradrenaline and dihydroxyphenylglycol were determined by high-performance liquid chromatography. The release of dihydroxyphenylglycol, the main neuronal noradrenaline metabolite, was used as an indicator of the free axoplasmic amine concentration. When storage function of neuronal vesicles was disturbed by Ro 4-1284 or trimethyltin, high dihydroxyphenylglycol release was observed without concomitant overflow of noradrenaline. If, however, these agents were combined with inhibition of Na+K+-ATPase or with veratridine-induced entry of sodium into the neuron, both dihydroxyphenylglycol and noradrenaline were released. Noradrenaline release was independent of extracellular calcium and was suppressed by blockade of neuronal catecholamine uptake (uptake1), indicating nonexocytotic noradrenaline liberation from the sympathetic nerve ending. This release critically depended on two conditions: 1) increased cytoplasmic concentrations of noradrenaline within the sympathetic neuron and 2) intraneuronal sodium accumulation. Both conditions together were required to induce noradrenaline efflux across the plasma membrane using the uptake1 carrier in reverse of its normal transport direction. A disturbed energy status of the sympathetic neuron, induced by cyanide intoxication or ischemia, likewise caused calcium-independent noradrenaline release by interfering with both vesicular storage function and neuronal sodium homoeostatis. Again, release was sensitive to uptake1 blockade. Since neuronal sodium accumulation was the rate-limiting step, release was further accelerated when residual Na+,K+-ATPase activity was inhibited. Na+-H+ exchange was identified as the predominant pathway of sodium entry into the sympathetic nerve ending in ischemia, and its inhibition by amiloride and ethylisopropylamiloride markedly suppressed ischemia-induced noradrenaline release.

Regulation of Nerve Growth Factor Sythesis/Secretion by Catecholamine in Cultured Mouse Astroglial Cells.

Abstract: The nerve growth factor (NGF) synthesis/secretion by cultured mouse astroglial cells was modulated by catecholamine. In quiescent cells, epinephrine (EN) and dopamine (DA) markedly increased the NGF content in the conditioned medium (CM). Conversely, EN, DA, and norepinephrine (NE) decreased the NGF content in growing cells. Cholinergic agonists, metacholine and carbamylcholine, slightly increased the NGF content in quiescent cells, but showed no effects on growing cells. Other neurotransmitters tested had no effects on either growing or quiescent cells. These results suggest that catecholamine is one of the molecules responsible for regulation of NGF synthesis/secretion in the mouse brain.

Some Pungent Principles of Spices Cause the Adrenal Medulla to Secrete Catecholamine in Anesthetized Rats

Abstract: We recently reported that ca'psaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the rat adrenal medulla. In this study, the effects of some pungent principles of spices on adrenal catecholamine secretion were investigated as compared with that of capsaicin. An increase in catecholamine, especially epinephrine, secretion was observed not only on capsaicin infusion but also on piperine (a pungent principle of pepper) and zingerone (ginger) infusion. Even on infusion of the same amount (650 nmol/kg, i.v.), the order of poten.cy as to catecholamine secretion was capsaicin >> piperine > zingerone. - While, sulfur-containing and volatile pungent principles, allylisothiocyanate (mustard, etc.) and diallyldisul- fide (garlic, etc.), did not even cause slight catecholamine secre- tion. Furthermore, these adrenergic secretagogues were readily transported via the gut into the body. These results indicate that some pungent principles of dietary spices can induce a warming action via adrenal catecholamine secretion. o 1988 Society for Experimental Biology and Medic inc

Decreased beta-adrenergic receptor density and catecholamine response in male cigarette smokers. A study of monozygotic twin pairs discordant for smoking.

Abstract: The effect of long-term cigarette smoking on beta-adrenoceptor density and catecholamine response was studied in 10 monozygotic male twin-pairs discordant for smoking, with an average discordance time for smoking of 23 years (range, 12-35 years). The density of beta-adrenergic receptors was 40% lower in the lymphocytes of smoking twins compared with their nonsmoking cotwins (beta-receptor density, 6.7 +/- 1.2 and 11.1 +/- 1.8 fmol/10(6) cells, respectively; p less than 0.05). The corresponding apparent Kd values were 31.7 +/- 5.5 and 26.7 +/- 5.4 pM, respectively. Stimulation of the lymphocyte beta-receptors resulted in significantly lower levels of cyclic adenosine monophosphate in the smokers compared with the nonsmokers (16.2 +/- 3.3 vs. 29.2 +/- 6.5 pmol/10(6) cells, p less than 0.05). When subjected to submaximal exercise, the smokers had a lower level of cyclic adenosine monophosphate in plasma (25.9 +/- 1.2 vs. 28.6 +/- 1.0, p less than 0.05) and a net decrease was seen in plasma free fatty acids in the smokers compared with a net increase in the nonsmokers (-15% vs. +19%, p less than 0.01). The total plasma catecholamine level was, in the basal state, significantly higher in smokers compared with nonsmokers (74.8%, p less than 0.05). The intrapair difference in plasma norepinephrine predicted well the intrapair difference in beta-receptor density (r = -0.84, p less than 0.001). We conclude that the autonomic neurohumoral response evoked by cigarette smoking results in downregulation of beta-adrenergic receptors in long-term smokers.

High NaCl diet reduces hypothalamic norepinephrine turnover in hypertensive rats.

Abstract: The current study tested the hypothesis that high NaCl diets elevate blood pressure in NaCl-sensitive spontaneously hypertensive rats (SHR-S) by reducing noradrenergic input to depressor neurons in the anterior hypothalamus. SHR-S were studied at 7 weeks of age, and age-matched salt resistant SHR (SHR-R) and normotensive Wistar-Kyoto rats (WKY) were controls. Rats were fed either high (8%) NaCl or control (1% NaCl) diets for 2 weeks, following which norepinephrine turnover in hypothalamus (anterior, posterior, and ventral regions), brainstem (pons and medulla), and thoracic spinal cord was assessed using the dopamine beta-hydroxylase inhibitor 1-cyclohexyl-2-mercapto-imidazole (CHMI). Regional brain catecholamines were measured by high performance liquid chromatography with electrochemical detection following intraperitoneal injection of CHMI or vehicle. Disappearance of norepinephrine following CHMI was used as an index of noradrenergic neuronal activity. The 8% NaCl diet caused a significant elevation in blood pressure in SHR-S but not in SHR-R or WKY. Endogenous norepinephrine levels and turnover were lower in the anterior hypothalamus of SHR-S fed 8% NaCl than in those fed 1% NaCl but were not significantly different in other groups. Endogenous norepinephrine levels and turnover were greater in pons of 8% NaCl--fed SHR-S than in those fed 1% NaCl but were not significantly different in other groups. These observations support the hypothesis that reduced noradrenergic input to depressor neurons in the anterior hypothalamus and increased noradrenergic input to neurons in the pons are related to NaCl sensitivity in the SHR-S.

Neuropeptide Y inhibits the nicotine-mediated release of catecholamines from bovine adrenal chromaffin cells.

Abstract: The possible role of neuropeptide Y (NPY) in catecholamine secretion was studied by using bovine adrenal chromaffin cells. NPY produced a concentration-dependent inhibition of nicotine-stimulated norepinephrine and epinephrine release from bovine chromaffin cells with IC50 (concentration of NPY which inhibits 50% of maximum release of catecholamines) values of 1.8 x 10(-9) M and 1.7 x 10(-9) M, respectively. Catecholamine release induced by 56 mM KCl was not inhibited by NPY at these concentrations but was inhibited by high concentration (2 x 10(-6) M) of NPY. This inhibition was not affected by the concentration of nicotine used for catecholamine release or the presence of alpha, beta adrenergic and muscarinic antagonists. A structurally related peptide, human pancreatic polypeptide, showed a similar inhibitory effect on catecholamine release, but peptide YY or avian pancreatic polypeptide had little or no effect. N-propionyl[3H]NPY binds to a single class of saturable binding sites on bovine adrenal medulla membranes with a KD = 0.32 +/- 0.07 nM and Bmax = 63 +/- 16 fmol/mg of protein. The rank order of potency of NPY and other structurally similar peptides to displace N-propionyl[3H]NPY from binding is human pancreatic polypeptide greater than or equal to NPY much greater than peptide YY greater than avian pancreatic polypeptide, and is correlated with their potency to inhibit catecholamine release. These results suggest a modulatory role for NPY through a specific NPY receptor in the secretion of catecholamine from the adrenal.

Exposure of striatal [corrected] synaptosomes to L-dopa increases levels of oxidized glutathione.

Abstract: Incubation of striatal synaptosomes with L-dopa and glucose in either the presence or absence of 10 microM reserpine resulted in a rise in the level of oxidized glutathione (GSSG) within the isolated tissue pellet. The rise in GSSG was concentration dependent in the range of 0.04-1.0 mM L-dopa. With 1.0 mM L-dopa in the presence of reserpine, the GSSG level was elevated by 7.0 +/- 0.7 pmol/mg original striatal tissue, which corresponds to an increase of 38.0 +/- 4.5% compared with control. The rise in GSSG reflects an oxidative stress. The oxidation of dopamine by monoamine oxidase generates H2O2, which is normally detoxified by glutathione peroxidase to yield GSSG. In the presence of clorgyline or pargyline (two monoamine oxidase inhibitors), the rise in GSSG was suppressed by 88-92%, as was the formation of DOPAC. NSD-1055 and carbidopa (two inhibitors of dopa-decarboxylase) also significantly suppressed (50-60%) the rise in GSSG. These data show that the synthesis of dopamine from L-dopa, with subsequent catabolism of dopamine, can evoke a significant rise in the level of GSSG, which reflects the oxidant stress associated with monoamine oxidase activity.