Showing papers on "Vasopressin published in 2000"
TL;DR: It is suggested that a variety of endocrine regulatory points exist whereby stress limits the efficiency of reproduction, and endocrine evidence to show that stressors interfere with precise timings of reproductive hormone release within the follicular phase.
519 citations
TL;DR: The data suggest that vasopressinergic regulation of the HPA axis is critical for sustaining corticotroph responsiveness in the presence of high circulating glucocorticoid levels during chronic stress.
353 citations
TL;DR: Results indicate that vasopressin induces cAMP-mediated vWF secretion by a direct effect on endothelial cells, and provides a cellular mechanism for the hemostatic effects of DDAVP.
Abstract: Vasopressin and its analogue 1-deamino-8-D-arginine vasopressin (DDAVP) are known to raise plasma von Willebrand factor (vWF) levels. DDAVP is used as a hemostatic agent for the treatment of von Willebrand's disease. However, its cellular mechanisms of action have not been elucidated. DDAVP, a specific agonist for the vasopressin V2 receptor (V2R), exerts its antidiuretic effect via a rise in cAMP in kidney collecting ducts. We tested the hypothesis that DDAVP induces vWF secretion by binding to V2R and activating cAMP-mediated signaling in endothelial cells. vWF secretion from human umbilical vein endothelial cells (HUVECs) can be mediated by cAMP, but DDAVP is ineffective, presumably due to the absence of V2R. We report that DDAVP stimulates vWF secretion in a cAMP-dependent manner in HUVECs after transfection of the V2R. In addition, vasopressin and DDAVP induce vWF secretion in human lung microvascular endothelial cells (HMVEC-L). These cells (but not HUVECs) express endogenous V2R, as shown by RT-PCR. Vasopressin-induced vWF secretion is mimicked by DDAVP and inhibited by the selective V2R antagonist SR121463B. It is mediated by cAMP, since it is inhibited by the protein kinase A inhibitor Rp-8CPT-cAMPS. These results indicate that vasopressin induces cAMP-mediated vWF secretion by a direct effect on endothelial cells. They also demonstrate functional expression of V2R in endothelial cells, and provide a cellular mechanism for the hemostatic effects of DDAVP.
253 citations
TL;DR: All three subunits of ENaC are upregulated by vasopressin with temporal and regional differences, but changes are too slow to play a major role in the short-term action of vasoppressin to stimulate sodium reabsorption in the collecting duct.
Abstract: Sodium transport is increased by vasopressin in the cortical collecting ducts of rats and rabbits. Here we investigate, by quantitative immunoblotting, the effects of vasopressin on abundances of the epithelial sodium channel (ENaC) subunits (alpha, beta, and gamma) in rat kidney. Seven-day infusion of 1-deamino-[8-D-arginine]-vasopressin (dDAVP) to Brattleboro rats markedly increased whole kidney abundances of beta- and gamma-ENaC (to 238% and 288% of vehicle, respectively), whereas alpha-ENaC was more modestly, yet significantly, increased (to 142% of vehicle). Similarly, 7-day water restriction in Sprague-Dawley rats resulted in significantly increased abundances of beta- and gamma- but no significant change in alpha-ENaC. Acute administration of dDAVP (2 nmol) to Brattleboro rats resulted in modest, but significant, increases in abundance for all ENaC subunits, within 1 h. In conclusion, all three subunits of ENaC are upregulated by vasopressin with temporal and regional differences. These changes are too slow to play a major role in the short-term action of vasopressin to stimulate sodium reabsorption in the collecting duct. Long-term increases in ENaC abundance should add to the short-term regulatory mechanisms (undefined in this study) to enhance sodium transport in the renal collecting duct.
229 citations
TL;DR: The results suggest that Ca2+ release from ryanodine-sensitive stores plays an essential role in vasopressin-mediated aquaporin-2 trafficking via a calmodulin-dependent mechanism.
226 citations
TL;DR: The role of taurine is extended from the regulation of cell volume to that of the whole body fluid balance, pointing to a new role of supraoptic glial cells as active components in a neuroendocrine regulatory loop.
190 citations
TL;DR: The long-term administration of analogs of vasopressin (ornipressin or terlipressin) or other vasoconstrictors together with plasma volume expansion with albumin is associated with a dramatic improvement in circulatory function and normalization of serum creatinine concentration in patients with severe hepatorenal syndrome.
175 citations
TL;DR: Monitoring of stress effects on corticotropin-releasing factor and AVP heteronuclear RNA expression in rats suggested that glucocorticoid negative feedback at the transcriptional levels is exerted selectively on AVP gene expression through a mechanism that likely involves glucocortex receptor interactions with immediate-early gene products.
Abstract: To identify molecular targets of corticosteroid negative feedback effects on neurosecretory neurons comprising the central limb of the hypothalamo-pituitary-adrenal (HPA) axis, we monitored ether stress effects on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) heteronuclear RNA (hnRNA) expression in rats that were intact or adrenalectomized (ADX) and replaced with corticosterone (B) at constant levels ranging from nil to peak stress concentrations. Under basal conditions, relative levels of both primary transcripts varied inversely as a function of plasma B titers. In response to stress, the kinetics of CRF hnRNA responses of intact and ADX rats replaced with low B were similar, peaking at 5 min after stress. By contrast, intact rats showed a delayed AVP hnRNA response (peak at 2 hr), the timing of which was markedly advanced in ADX/low B-replaced animals (peak at 5-30 min). Transcription factors implicated in these responses responded similarly. Manipulation of B status did not affect the early (5-15 min) phosphorylation of transcription factor cAMP-response element-binding protein (CREB) but accelerated maximal Fos induction from 2 hr after stress (intact) to 1 hr (ADX). Assays of binding by proteins in hypothalamic extracts of similarly manipulated rats toward consensus CRE and AP-1 response elements supported a role for the stress-induced plasma B increment in antagonizing AP-1, but not CRE, binding. These findings suggest that glucocorticoid negative feedback at the transcriptional levels is exerted selectively on AVP gene expression through a mechanism that likely involves glucocorticoid receptor interactions with immediate-early gene products.
174 citations
TL;DR: The effect of CART on CRH neurons most likely leads to corticosterone secretion from the adrenal gland, which may contribute to the inhibitory effects of Cart on feeding behavior and c-Fos as a marker of neuronal activity.
Abstract: We have recently shown that intracerebroventricular (i.c.v.) administration of the hypothalamic neuropeptide cocaine-amphetamine-regulated transcript (CART) inhibits food intake and induces the expression of c-fos in several nuclei involved in the regulation of food intake. A high number of CART-induced c-Fos-positive nuclei in the paraventricular nucleus of the hypothalamus prompted us to examine the effect of i.c.v. recombinant CART-(42-89) on activation of CRH-, oxytocin-, and vasopressin-synthesizing neuroendocrine cells in the paraventricular nucleus (PVN). In addition, plasma levels of glucose were examined after central administration of CART-(42-89). Seventy-six male Wistar rats were fitted with i.c.v. cannulas and singly housed under 12-h light, 12-h dark conditions. One week postsurgery the animals were injected i.c.v. in the morning with 0.5 microg recombinant CART-(42-89) or saline. Trunk blood was collected by decapitation at 0 (baseline), 10, 20, 40, 60, 120, or 240 min. CART caused a strong increase in circulating corticosterone that was significantly different from saline at 20, 40, 60, and 120 min postinjection (P<0.05). Furthermore, CART caused a transient rise in plasma oxytocin levels (P<0.05 at 10 and 20 min postinjection), whereas plasma vasopressin levels were unaffected by i.c.v. CART. Animals injected i.c.v. with CART showed a rise in blood glucose levels 10 min postinjection (P<0.05). To examine whether the stimulatory effect of i.c.v. CART on corticosterone and oxytocin secretion is caused by activation of paraventricular nucleus/supraoptic nucleus (PVN/SON) neuroendocrine neurons, we used c-Fos as a marker of neuronal activity. Animals injected with CART showed a strong increase in c-Fos-immunoreactive nuclei in the PVN. Double immunohistochemistry revealed that a high (89+/-0.4%) number of CRH-immunoreactive neurons in the PVN contained c-Fos after CART i.c.v.. c-Fos expression was also observed in oxytocinergic cells (in both magnocellular and parvicellular PVN neurons as well as in the supraoptic nuclei) 120 min after CART administration, whereas none of the vasopressinergic neurons contained c-Fos. Triple immunofluorescence microscopy revealed that CART-immunoreactive fibers closely apposed c-Fos-positive CRH neurons, suggestive of a direct action of CART on PVN CRH neurons. In summary, i.c.v. CART activates central CRH neurons as well as both magnocellular (presumably neurohypophysial) and parvicellular (presumably descending) oxytocinergic neurons of the PVN. The effect of CART on CRH neurons most likely leads to corticosterone secretion from the adrenal gland, which may contribute to the inhibitory effects of CART on feeding behavior.
165 citations
TL;DR: These data provide the first in vivo evidence that acute rTMS of frontal brain regions has a differentiated modulatory effect on selected neurotransmitter/neuromodulator systems in distinct brain areas.
Abstract: Using intracerebral microdialysis in urethane-anaesthetized adult male Wistar rats, we monitored the effects of acute repetitive transcranial magnetic stimulation (rTMS; 20 trains of 20 Hz, 2.5 s) on the intrahypothalamic release of arginine vasopressin (AVP) and selected amino acids (glutamate, glutamine, aspartate, serine, arginine, taurine, gamma-aminobutyric acid) and the intrahippocampal release of monoamines (dopamine, noradrenaline, serotonin) and their metabolites (homovanillic acid, 3,4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid). The stimulation parameters were adjusted according to the results of accurate computer reconstructions of the current density distributions induced by rTMS in the rat and human brains, ensuring similar stimulation patterns in both cases. There was a continuous reduction in AVP release of up to 50% within the hypothalamic paraventricular nucleus in response to rTMS. In contrast, the release of taurine, aspartate and serine was selectively stimulated within this nucleus by rTMS. Furthermore, in the dorsal hippocampus the extracellular concentration of dopamine was elevated in response to rTMS. Taken together, these data provide the first in vivo evidence that acute rTMS of frontal brain regions has a differentiated modulatory effect on selected neurotransmitter/neuromodulator systems in distinct brain areas.
160 citations
TL;DR: Vasopressin at low doses to be a safe and an effective vasopressor in 50 patients with postcardiotomy vasodilatory shock is demonstrated.
TL;DR: In this paper, the expression of vasopressin (AVP) mRNA in the human suprachiasmatic nucleus (SCN) was investigated and it was shown that the amount of AVP mRNA expressed as masked silver grains in the SCN was 3 times lower in AD patients than in age-and time-of-death-matched controls.
Abstract: Circadian rhythm disturbances are frequently present in Alzheimer disease (AD). In the present study, we investigated the expression of vasopressin (AVP) mRNA in the human suprachiasmatic nucleus (SCN). The in situ hybridization procedure on formalin-fixed paraffin-embedded material was improved to such a degree that we could, for the first time, visualize AVP mRNA expressing neurons in the human SCN and carry out quantitative measurements. The total amount of AVP mRNA expressed as masked silver grains in the SCN was 3 times lower in AD patients (n = 14; 2,135 +/- 597 microm2) than in age- and time-of-death-matched controls (n = 11; 6,667 +/- 1466 microm2) (p = 0.003). No significant difference was found in the amount of AVP mRNA between AD patients with depression (n = 7) and without depression (n = 7) (2,985 +/-1103 microm2 and 1,285 +/- 298 microm2, respectively; p = 0.38). In addition, the human SCN AVP mRNA expressing neurons showed a marked day-night difference in controls under 80 years of age. The amount of AVP mRNA was more than 3 times higher during the daytime (9,028 +/- 1709 microm2, n = 7) than at night (2,536 +/- 740 microm2, n = 4; p = 0.02), whereas no clear diurnal rhythm of AVP mRNA in the SCN was observed in AD patients. There was no relationship between the amount of AVP mRNA in the SCN and age at onset of dementia, duration of AD and the neuropathological changes in the cerebral cortex. These findings suggest that the neurobiological basis of the circadian rhythm disturbances that are responsible for behavioral rhythm disorders is located in the SCN. It also explains the beneficial effects of light therapy on nightly restlessness in AD patients.
TL;DR: During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.
TL;DR: The data indicate that recruitment of AQP2 to the plasma membrane and its retrieval to a pool of intracellular vesicles may be regulated independently, PGE(2) may counteract AVP action by activation of AQp2 retrieval, and dephosphorylation of AQ P2 is not a prerequisite for its internalization.
Abstract: Prostaglandin E2 (PGE2) antagonizes the action of arginine vasopressin (AVP) on collecting duct water permeability. To investigate the mechanism of this antagonism, rat renal inner medulla (IM) was...
TL;DR: Modest maternal undernutrition during pregnancy alters development of the cardiovascular system, producing elevated blood pressure in postnatal life and the HPA axis is altered, with reduced activity during fetal life, but increased activity postnatally.
Abstract: The effect of a 15% reduction in maternal nutrition for the first 70 days of gestation on cardiovascular and hypothalamic–pituitary–adrenal (HPA) axis responses to administration of corticotropin releasing hormone (CRH) + arginine vasopressin (AVP) was studied at 128 0.7 days gestation in fetal sheep and postnatally, at 85 4.5 days in young lambs. The effect on the fetal cardiovascular response to acute hypoxaemia was also examined. Under basal conditions, fetal heart rate (FHR) was reduced (P<0.05) and basal femoral artery vascular resistance (FVR) was increased (P<0.05) in fetuses of dietary-restricted (R) ewes compared with controls (C). Fetal mean arterial pressure (MAP) was similar in both groups. Femoral artery vascular resistance was also greater during hypoxaemia in R fetuses compared with C fetuses (P<0.05), suggesting that chemoreflex mechanisms were augmented in the R group. The fetal ACTH response to CRH + AVP was similar in both groups. However, cortisol responses to CRH + AVP were smaller in R fetuses compared with C fetuses (P<0.05). Postnatally, basal MAP (P<0.05), and ACTH (P<0.01) and cortisol (P<0.001) responses were greater in R lambs compared with C lambs. It was concluded that modest maternal undernutrition during pregnancy alters development of the cardiovascular system, producing elevated blood pressure in postnatal life. Development of the HPA axis is also altered, with reduced activity during fetal life, but increased activity postnatally. The data suggest that the HPA axis may play a role in mediating the elevation of MAP in R lambs.
TL;DR: In this paper, the protein and mRNA expression levels of the glial water channel aquaporin-4 (AQP4) undergo downregulation and whether there is a subcellular redistribution of AQP4 protein in rat brain in response to systemic hyponatremia and brain edema.
TL;DR: It is demonstrated that emotional stress activates the septal oxytocinergic, but not vasopressinerg, system and the physiological significance of intraseptally released OXT remains unclear.
TL;DR: Administration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation and return of spontaneous circulation was significantly more likely in epinphrine-treated pigs than in animals resuscitated with vasOPressin alone.
Abstract: ObjectiveThis study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest.DesignProspective, randomized laboratory investi
TL;DR: The results demonstrate that combined physical and emotional stress selectively triggers the release of vasopressin within all brain areas under study but not into the general circulation, and the observed dissociation between central and peripheral nonapeptide release supports the hypothesis that plasma vasoppressin and oxytocin concentrations do not necessarily reflect central release patterns.
Abstract: The two nonapeptides arginine vasopressin and oxytocin are not only secreted from the neurohypophysis into the general circulation but are also released intracerebrally. Our recent research has focused on the release patterns and effects of oxytocin and vasopressin in brain areas, such as the septum and hypothalamus, that are thought to be involved in the regulation of (1) behavioural responses and (2) responses of the hypothalamo-neurohypophysial system (HNS) to stressor exposure in rats. The results demonstrate that combined physical and emotional stress (induced by exposure to forced swimming) selectively triggers the release of vasopressin within all brain areas under study but not into the general circulation. Under emotional stress conditions (induced by exposure to the 'social defeat' procedure), however, oxytocin rather than vasopressin release increased within the hypothalamus and septum. Experiments aimed at revealing the neuroendocrine and behavioural relevance of the local nonapeptide release provided evidence for an involvement of vasopressin in the regulation of HNS activity (within the hypothalamus) and, moreover, in acute stress-coping strategies, anxiety-related behaviour and learning and memory processes (within the septum). The observed dissociation between central and peripheral nonapeptide release not only supports the hypothesis that plasma vasopressin and oxytocin concentrations do not necessarily reflect central release patterns but also suggests vasopressin and oxytocin neurones are able to independently release their nonapeptide from different parts of their neuronal surface (e.g. from somata/dendrites vs. axon terminals). This remarkable regulatory capacity provides the basis for an differential involvement of vasopressin, and probably also oxytocin, in the co-ordination of neuroendocrine activity, emotionality and cognition at different brain levels to ensure an appropriate behavioural response of the organism to stressful stimuli.
TL;DR: It is concluded that stimulation of Na(+/K+)-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.
Abstract: . In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased Na + /K + -ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of Na + /K + -ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and Na + /K + -ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl 2 nephropathy. The role of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD Na + /K + -ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD Na + /K + -ATPase. It is concluded that stimulation of Na + /K + -ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.
TL;DR: It is suggested that vasopressin directly induces myocyte hypertrophic growth via the V(1A) receptor in neonatal rat heart cells.
TL;DR: Exposure to anabolic-androgenic steroids during adolescent development predisposes hamsters to heightened levels of aggressive behavior by influencing the anterior hypothalamic-arginine vasopressin (AH-AVP) neural system, providing direct evidence for a causal role of AH-A VP expression and function in early onset AAS-stimulated aggression.
TL;DR: A strong decrease of ERbeta and an increase of ERalpha immunoreactivity in AVP neurons of the dl-SON of postmenopausal women are demonstrated for the first time and both receptor changes are proposed to participate in the activation of the AVP neuron in post menopausal women.
Abstract: The dorsolateral supraoptic nucleus (dl-SON) is the main production site of plasma arginine vasopressin (AVP). Plasma AVP levels and the activity of AVP neurons in humans are higher in males than in premenopausal females. On the other hand, an increased activity of AVP neurons becomes prominent in postmenopausal women who have strongly decreased estrogen levels. As estrogens are presumed to inhibit AVP production in a receptor-mediated way, we studied estrogen receptor (ER) alpha and beta immunoreactivity in the dl-SON. Hypothalami of 34 controls were subdivided into 4 groups within a 50-yr boundary (young men, young women, elderly men, and elderly women). The AVP part of the dl-SON of young women contained 50 times more neurons with ERbeta nuclear staining than that in young men and 250 times more than that in elderly women. In addition, young women also showed more ERbeta cytoplasmic staining than young men and elderly women. In contrast to the ERbeta immunoreactivity, no differences were found in the number of ERalpha-positive neurons in the 4 groups, but the age and sex pattern of ERalpha staining was basically opposite that of ERbeta. Significant correlations between the percentage of ERbeta- and ERalpha-positive and -negative AVP neurons and age were found in women, but not in men. Our data demonstrate for the first time a strong decrease of ERbeta and an increase of ERalpha immunoreactivity in AVP neurons of the dl-SON of postmenopausal women. Both receptor changes are proposed to participate in the activation of the AVP neurons in postmenopausal women.
TL;DR: The study suggests that a typical hypothalamic-pituitary-adrenal axis is present in free-ranging bottlenose dolphins, and the relatively short capture and restraint times did not induce a significant neuroendocrine stress response.
Abstract: Marine mammals are routinely caught in the wild in an effort to monitor their health. However, capture-associated stress could potentially bias various biochemical parameters used to monitor the health of these wild caught animals. Therefore, the effects of capture were quantified by measuring plasma adrenal steroids and arginine vasopressin (AVP) in free-ranging bottlenose dolphins (Tursiops truncatus) (n=31). Total capture and restraint times were also correlated to hormone concentrations to quantify the effects of capture. Significant, positive correlations between corticosterone and cortisol (R=0.752; P<0.0001), and between corticosterone and aldosterone (R=0.441; P=0.045) were demonstrated. Significant correlations between capture and restraint time and hormone levels were not observed. Animals restrained for less than 20 min exhibited hormone levels similar to those for animals restrained for more than 20 min. The positive correlations among the adrenal steroids suggest that release of these steroids was stimulated by adrenocorticotropin (ACTH). The lack of a correlation between cortisol and AVP indicates that AVP did not influence ACTH-induced cortisol release in this situation. The study suggests that (1) a typical hypothalamic-pituitary-adrenal axis is present in these animals, and (2) the relatively short capture and restraint times did not induce a significant neuroendocrine stress response.
TL;DR: A selective compensatory activation of the hypothalamic vasopressinergic, but not the oxytocinergic system, is revealed to maintain basal ACTH secretion and HPA system activity in Crhr1-/- mutants.
Abstract: Deficiency of CRH receptor 1 (CRHR1) severely impairs the stress response of the hypothalamic-pituitary-adrenocortical (HPA) system and reduces anxiety-related behavior in mice. Intriguingly, in mice deficient for the CRHR1 (Crhr1-/-), basal plasma levels of ACTH are normal, suggesting the presence of compensatory mechanisms for pituitary ACTH secretion. We therefore studied the impact of the hypothalamic neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) on HPA system regulation in homozygous and heterozygous Crhr1 mutants under basal and different stress conditions. Basal plasma AVP concentrations were significantly elevated in Crhr1-/- mice. AVP messenger RNA expression was increased in the paraventricular nucleus of Crhr1-/- mutants together with a marked increase in AVP-like immunoreactivity in the median eminence. Administration of an AVP V1-receptor antagonist significantly decreased basal plasma ACTH levels in mutant mice. After continuous treatment with corticosterone, plasma AVP levels in homozygous Crhr1-/- mice were indistinguishable from those in wild-type littermates, thus providing evidence that glucocorticoid deficiency is the major driving force behind compensatory activation of the vasopressinergic system in Crhr1-/- mice. Neither plasma OXT levels under several different conditions nor OXT messenger RNA expression in the paraventricular nucleus were different between the genotypes. Taken together, our data reveal a selective compensatory activation of the hypothalamic vasopressinergic, but not the oxytocinergic system, to maintain basal ACTH secretion and HPA system activity in Crhr1-/- mutants.
TL;DR: Data suggest that P2X receptor activation, PKC-mediated phosphorylation, and gene transcription are required for the synergistic response of ATP and PE on oxytocin release, which is probably important to achieve sustained increases in plasma VP in response to prolonged hypotension.
Abstract: The A1 catecholamine neurons of the caudal ventrolateral medulla transmit hemodynamic information to the vasopressin (VP) neurons in the hypothalamus. These neurons corelease ATP with norepinephrine. Perifused explants of the hypothalamoneurohypophyseal system were used to investigate the role of these substances on VP release. ATP (100 micrometer) increased VP release 1.5-fold (p = 0.027). The response was rapid but unsustained. It was blocked by the P(2) receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). The alpha(1)-adrenergic agonist phenylephrine (PE; 100 micrometer) also increased VP release by 1.5-fold (p = 0.014). Again, the response was rapid and unsustained. However, simultaneous perifusion of explants with ATP (100 micrometer) and PE (100 micrometer) resulted in a threefold to fourfold increase in VP release, which was sustained for as long as 4 hr. There was a similar synergistic effect of ATP and PE on oxytocin release. Interestingly, the synergistic response was delayed approximately 40 min relative to the response to either agent alone. Several experiments were performed to elucidate the cellular mechanisms of this synergism. The effect was blocked by PPADS, a protein kinase C inhibitor (bisindolylmaleimide I HCl), and actinomycin, an inhibitor of gene transcription. These data suggest that P(2X) receptor activation, PKC-mediated phosphorylation, and gene transcription are required for the synergistic response. The marked synergism of these coreleased agents is probably important to achieve sustained increases in plasma VP in response to prolonged hypotension. These observations may also have broad applications to CNS function, because ATP may be coreleased at noradrenergic synapses throughout the CNS.
TL;DR: The authors used an in vitro hypothalamic brain slice preparation and whole cell and perforated patch recording to examine the response of magnocellular neurons in hypothalamic paraventricular cells.
Abstract: This investigation used an in vitro hypothalamic brain slice preparation and whole cell and perforated-patch recording to examine the response of magnocellular neurons in hypothalamic paraventricul...
TL;DR: The data indicate that the vasopressinergic cells in the SCN contain circadian oscillators, whose rhythms run mutually synchronized in the authors' cultures.
TL;DR: It is suggested that intracerebroventricular leptin acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.
Abstract: We determined the cardiovascular and neurohormonal responses to intracerebroventricular injection of leptin in conscious rabbits. Intracerebroventricular injection of leptin elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity while producing no consistent, significant increases in heart rate. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 50 μg of leptin (+17.3 ± 1.2 mmHg and +47.9 ± 12.0%) were obtained at 10 and 20 min after injection, respectively. Plasma catecholamine concentrations significantly increased at 60 min after intracerebroventricular injection of leptin (control vs. 60 min; epinephrine: 33 ± 12 vs. 97 ± 27 pg/ml, P < 0.05; norepinephrine: 298 ± 39 vs. 503 ± 86 pg/ml, P < 0.05). Intracerebroventricular injection of leptin also caused significant increases in plasma vasopressin and glucose levels. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a g...
TL;DR: It is shown by immunohistochemistry that TFF3 is localized to a distinct population of neurons of the human hypothalamic paraventricular and supraoptic nuclei.
Abstract: TFF-peptides (formerly P domain peptides, trefoil factors) are typical secretory products of many mucous epithelial cells. TFF3 is also synthesized in the hypothalamus and has anxiolytic or anxioge...