Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ingestion of ethanol results in a decreased level of plasma vasopressin, which appears to be caused by inhibition of arginine vasopressin (AVP) release from the neurohypophysis. Activation of membrane voltage-gated Ca2+ channels plays an important role in triggering this neurohormone release. In this article, single-channel recordings are used to demonstrate that ethanol, at concentrations constituting legal intoxication, inhibits dihydropyridine-sensitive "L-type" Ca2+ channels in isolated nerve terminals of the rat neurohypophysis. Ethanol reduced the channel open probability in a concentration-dependent manner. To allow finer resolution of channel openings and to better characterize the mechanisms of ethanol action, Bay K 8644 was used to prolong the openings of L-type Ca2+ channels. In the presence of this dihydropyridine (DHP), the reduction of the channel open probability by concentrations of ethanol of 25 mM or higher could be determined to be due primarily, although not completely, to a shortening of the open duration of this L-channel. Channel conductance was unaffected by ethanol, even at high concentrations. These results are consistent with previous macroscopic data indicating that calcium channels in these peptidergic terminals are targets for ethanol action, and indicate that ethanol acts directly on the gating characteristics of the L-type channel. Furthermore, examination of open and closed state transitions, as well as Hill plot analysis, suggests that ethanol's effects on gating are consistent with the interaction of a single drug molecule with a single target site, possibly the L-channel itself.
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PMID:Ethanol directly modulates gating of a dihydropyridine-sensitive Ca2+ channel in neurohypophysial terminals. 752 10

Ethanol ingestion affects the hypothalamo-neurohypophysial system resulting in increased diuresis, dehydration and hyperosmolality. We studied the supraoptic nucleus, of the hypothalamus, in ethanol-treated rats, to determine if ethanol alone and/or the associated disturbances of water metabolism lead to structural alterations in a nucleus known to play a central role in fluid homeostasis. Groups of male and female rats were ethanol-treated until 12 and 18 months of age and compared with age-matched pair-fed controls. Twelve and 18-month-old control groups and 12-month-old water control groups (rats submitted to chronic dehydration) were also included in this study in an attempt to differentiate between the effects of undernutrition and dehydration/hyperosmolality, and the specific neurotoxic effects of ethanol. We estimated the volume of the supraoptic nucleus and the numerical density of its neurons and calculated the total number of supraoptic neurons. The volume of both supraoptic neurons and neuropil were also estimated. In immunostained material the ratio of vasopressin to oxytocin neurons and the cross-sectional areas of the two neuronal types were evaluated. There was marked neuronal loss in alcohol-treated rats, but the volume of the supraoptic nucleus was increased. The increase in the volume of the supraoptic nucleus correlated with and was due to increases in the volume was particularly marked for vasopressin neurons. No significant differences were found between controls and pair-fed controls in any of the parameters investigated. In water control rats, the volume of the supraoptic nucleus and of the supraoptic neurons and neuropil was also greater than in pair-fed controls. However, the variations found were not as marked as in ethanol-treated rats and there was no cell loss. These findings reveal, for the first time, that chronic ethanol consumption affects the morphology of supraoptic neurons and neuropil and, consequently, the structure of the entire supraoptic nucleus. Moreover, this study supports the view that ethanol has direct neurotoxic effects on supraoptic neurons because the alterations that occur are not mimicked in animals in which water metabolism alone is disturbed.
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PMID:Effects of chronic alcohol consumption and of dehydration on the supraoptic nucleus of adult male and female rats. 825 26

Activation of phospholipase D (PLD) by receptor-coupled stimuli (vasopressin, ATP), phorbol esters, and Ca2+ ionophores was studied in isolated rat hepatocytes, double labeled with [3H]arachidonate and [14C]stearate. Phosphatidylethanol (Peth) was formed when cells were stimulated in the presence of ethanol. The effect of combinations of agonists was not additive, indicating that the same PLD isozyme(s) were activated. With all agonists, the 3H- and 14C-specific radioactivity in Peth was higher than in any of the main phospholipid classes. The 3H/14C ratios of Peth and phosphatidylcholine (PC) were identical and differed from other phospholipid classes, indicating that the predominant PLD substrate was a PC pool labeled preferentially with radioactive fatty acids. Ethanol (50-300 mM) decreased the initial rate of phosphatidic acid (PA) formation, but did not affect total PLD activity. Agonist-induced changes in steady state accumulation of PA or 1,2-diacylglycerol were also unaffected. A slow degradation of Peth (apparent t1/2 > 60 min) occurred after ethanol removal from cells prestimulated with vasopressin. The rate of degradation was unaffected by agonists that stimulate PLD. Thus, Peth formation is a suitable cumulative indicator for PLD activation in intact hepatocytes. Peth accumulation declined over a period of 5-20 min, depending on the agonist. The decline was not due to increased Peth degradation, or limitations in substrate supply to PLD, or enzyme inhibition by accumulated Peth. Instead, a homologous desensitization of PLD occurs with all agonists. This desensitization may involve the action of selective protein kinase C isozymes.
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PMID:Activation and desensitization of phospholipase D in intact rat hepatocytes. 828 37

Since ethanol ingestion is associated with a disruption of water and electrolyte balance in a variety of species, we sought to evaluate the regulatory control of atrial natriuretic peptide (ANP) in response to acute doses of ethanol. Male Sprague-Dawley rats were administered a 5-g/kg dose of ethanol (40% w/v) via a gastric tube, while control animals received an equivalent volume of water. Expressed as a percentage of control, plasma ANP levels were 39.0%, 28.5%, and 23.6% in the ethanol-treated animals at 30, 60, and 120 min postintubation, respectively. Ethanol-treated animals displayed blood alcohol concentrations of 89.0, 137.6, and 214.1 mg/dl at the same time periods. After 120 min, plasma renin activity was elevated from 8.7 to 20.3 ng/ml/h in conjunction with an increase in the levels of circulating aldosterone from 16.3 to 42.5 ng/dl and an increase in plasma vasopressin from 2.2 to 3.6 pg/ml. Levels of atrial ANP mRNA remained consistent over the time course of the experiment, and no changes in the amount of ventricular ANP transcript were observed. Tissue ANP levels were similar between ethanol-treated and water-loaded control animals. In vitro experiments using cultured cardiac myocytes suggest that ethanol exposure may not directly affect ANP secretion. We propose that acute ethanol treatment may inhibit atrial distension and subsequently modify the control of ANP release under volume loading conditions.
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PMID:Acute ethanol ingestion modifies the circulating plasma levels of atrial natriuretic peptide. 839 78

Large conductance, Ca(2+)-activated K+ channels are believed to underlie interburst intervals and, thus, contribute to the control of hormone release from neurohypophysial terminals. Because ethanol inhibits the release of vasopressin and oxytocin, we studied its effects on large conductance, Ca(2+)-activated K+ channels from these terminals using patch-clamp techniques. Ethanol (10-100 mM) applied to the cytosolic surface of excised, inside-out patches reversibly increases channel activity in a concentration-dependent manner, reaching a plateau at 50-100 mM. This activation is not mediated by freely diffusible cytosolic second messengers or the release of Ca2+ from intracellular stores. Rather, it likely reflects a direct interaction of ethanol with the channel protein or a closely associated component. Neither the unitary conductance nor the characteristics of the voltage-current relationship are modified by the drug. The increase of channel activity by ethanol results from a modification of channel gating properties: the contribution of long openings to the total time spent in the open state is increased, the average duration of the fast openings is slightly increased, and long closures disappear in the presence of the drug. The activation of large conductance, Ca(2+)-activated K+ channels by ethanol, in conjunction with the previously reported inhibition of voltage-dependent Ca2+ channels, can explain the reduced release of vasopressin and oxytocin after ethanol ingestion.
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PMID:Ethanol increases the activity of large conductance, Ca(2+)-activated K+ channels in isolated neurohypophysial terminals. 856 10

Phospholipase C (PLC)-mediated signal transduction processes in rat hepatocytes are subject to modulation by protein phosphatases (PPases) and protein kinases, including protein kinase A (PKA) and protein kinase C. Ethanol (EtOH) stimulates PLC activity in liver cells in the absence of hormones, and EtOH pretreatment inhibits the subsequent stimulation of PLC by hormonal stimuli. There is evidence that protein kinase activities are involved in these actions of EtOH. We investigated the effects of okadaic acid (OKA), a PPase inhibitor, and 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt-cAMP), a cell permeant cAMP analog that activates PKA, on EtOH-induced PLC activation. In addition, we studied the combined effects of cpt-cAMP and EtOH/OKA on vasopressin-induced PLC activation. PLC activation (cytosolic Ca2+ mobilization and inositol trisphosphate accumulation) induced by EtOH and vasopressin was inhibited by treatment with OKA, and was potentiated by cpt-cAMP. OKA treatment prevented the effect of cpt-cAMP. Pretreatment with EtOH caused inhibition of vasopressin-induced PLC activation. EtOH also decreased the enhancing effect of cpt-cAMP on the responses to vasopressin. The susceptibility to enhancement by cpt-cAMP plotted as a function of the initial rate of vasopressin-induced Ca2+ mobilization in EtOH-treated cells was similar to the pattern observed in OKA-treated cells. These data suggest that interactions of OKA and PKA on EtOH-induced PLC activation occurred at the level of G-protein, and indicate that EtOH may act as an inhibitory agent of PPase.
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PMID:Interaction of protein phosphatases and ethanol on phospholipase C-mediated intracellular signal transduction processes in rat hepatocytes: role of protein kinase A. 898 30

Ethanol (EtOH) reversibly activates large conductance, Ca(++)-activated K+ (BK) channels in rat neurohypophysial terminals, an effect that probably contributes to the inhibition of vasopressin release by this drug. Heterogeneity in the terminal channel population makes it difficult to determine the mechanisms underlying this activation. Here, we report the effects of EtOH on the steady-state activity of BK channels cloned from mouse brain (mslo, alpha subunit) and expressed in Xenopus oocytes. EtOH reversibly increased mslo channel activity in excised patches, showing a potency (EC50 = 24 mM) similar to that reported using native channels. EtOH activation was observed under conditions that make it highly improbable that it is mediated by freely diffusible second messengers, or secondary to G-protein modulation. Rather, it probably results from a functional interaction between the drug and the channel alpha subunit. Activation occurred without increase in the number of functional channels present in the patch and resulted from actions that were a function of EtOH concentration: at < or = 10 mM, activation was due to a decrease in the channel mean closed time, whereas between 25 and 100 mM, activation was due to both a decrease in the mean closed time and an increase in the mean open time. The characteristic high unitary conductance and ionic selectivity of BK channels were unaltered by the drug. Whereas the voltage dependence of channel gating remained unchanged, channel activation mediated by the response of the Ca(++)-sensing site(s) to increases in the concentration of intracellular calcium, [Ca++]ic, was reduced by EtOH. This finding is consistent with EtOH and [Ca++]ic behaving functionally as partial and full agonists of mslo channels, respectively. Because the potentiation of mslo activity by the drug decreased as Ca++ levels were increased, EtOH-activation of BK channels would be most evident when [Ca++]ic is near resting levels, rather than during periods of high activity and Ca++ influx.
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PMID:Ethanol increases the activity of Ca(++)-dependent K+ (mslo) channels: functional interaction with cytosolic Ca++. 943 86

The ability of alcohol to activate the hypothalamic-pituitary-adrenal (HPA) axis is well documented in investigations based in acute and short-term experimental paradigms. Herein, we have addressed the possibility that the prolonged exposure to ethanol concentrations that are initially effective in stimulating corticosteroid secretion might induce alterations in the response of the HPA axis that cannot be evinced by shorter exposures. Using conventional histological techniques, immunohistochemistry and in situ hybridization, we have examined the medial parvocellular division of the paraventricular nucleus (PVNmp), and the synthesis and expression of corticotropin-releasing hormone (CRH) and vasopressin (VP) by its constituent neurons, in rats submitted to 6 months of ethanol treatment and to withdrawal (2 months after 6 months of alcohol intake). Ethanol treatment and withdrawal did not produce neuronal loss in the PVNmp. However, the total number of CRH- and VP-immunoreactive neurons and the CRH mRNA levels were significantly decreased by ethanol treatment. In withdrawn rats, the number of CRH- and VP-immunostained neurons and the gene expression of CRH were increased relative to ethanol-treated rats and did not differ from those of controls. No significant variations were detected in VP mRNA levels as a result of ethanol treatment or withdrawal. These results show that prolonged alcohol intake blunts the expression of CRH and VP in the parvocellular neurons of the PVN, and that this effect is, partially at least, reversible by withdrawal. They also suggest that the development of tolerance to the effects of ethanol involve changes that take place at the hypothalamic level.
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PMID:Prolonged alcohol intake leads to reversible depression of corticotropin-releasing hormone and vasopressin immunoreactivity and mRNA levels in the parvocellular neurons of the paraventricular nucleus. 1239 36

This study evaluates the effect of prolonged ethanol ingestion on the renal ability to concentrate urine. Suckling Wistar rats born to mothers given ethanol before and during gestation and suckling periods (ethanol-exposed offspring) were used and the results were compared with those obtained from offspring of dams given diets containing no ethanol. Comparisons were also made between progenitors with or without prolonged ethanol ingestion. Body and kidney weights; arginine-vasopressin (AVP) and aldosterone plasma levels; plasma, urine and renal papillary osmolality; urine outflow; kidney AQP2, AQP3 and AQP4 expression and diencephalon AVP mRNA expression were determined. As compared with control offspring, the ethanol-exposed offspring present i) lower body and kidney weights; ii) lower urine outflow; iii) higher renal AQP2 and AQP3 mRNA; iv) higher renal AQP2 protein content and v) higher urine and renal papillary osmolality. These changes were also observed in the ethanol-treated progenitors, although they were of smaller magnitude. Plasma osmolality, renal AQP4 mRNA, AVP plasma levels and diencephalon AVP mRNA expression were not affected by the ethanol treatment. Plasma levels of aldosterone were only significantly increased in the ethanol-exposed suckling rats. It is concluded that maternal ethanol ingestion before and during gestation and suckling periods affects the renal function of the offspring, up-regulating renal AQP2 expression by an AVP-independent mechanism. Ethanol-treated progenitors manifest similar renal changes, although of lesser magnitude than the offspring.
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PMID:Prolonged ethanol ingestion increases renal AQP2 and AQP3 expression in adult rats and in their offspring. 1513 48

Abstract We tested the hypothesis of a cross-inhibition of oxytocin (OT) release by endogenous opioid peptides co-released with vasopressin (VP). This opioid cross-inhibition resulted in a selective block of OT release and hence in preferential release of VP. The effects of the opiate receptor antagonist naloxone were tested on neurohypophyseal VP release during dehydration, ethanol administration and sulphated cholecystokinin octapeptide (CCK-8S) application, assuming that the inhibition of pituitary OT release by endogenous opioids increases as neurohypophyseal VP output increases. A high VP output was found to coincide with increased inhibition of OT release: Subcutaneous injection of graded doses of naloxone (30 min prior to decapitation), augmented OT plasma levels significantly more in 24 h water-deprived male rats than in normally hydrated rats. Naloxone had no effect on VP release. Ethanol (10% in saline) administered intragastrically 50 min prior to decapitation and 20 min before subcutaneous naloxone (5 mg/kg) resulted in the inhibition of VP output. The ethanol treatment resulted in a rise in plasma OT levels that was additional to the effect of naloxone. These features were present in normally hydrated as well as in 24 h water-deprived animals, but were more pronounced in the latter group. Peripheral CCK-8S administration induces an abrupt and selective secretion of OT. Blocking the opioid inhibition of OT release with naloxone resulted in a significant rise of OT compared to that with CCK-8S alone. The magnitude of the opioid inhibition coincided with the activity of the VP system, and a higher dose of naloxone was needed to potentiate the CCK-8S effect on OT release in the water-deprived group than in euhydrated rats. No effect of CCK-8S and/or naloxone was found on VP plasma levels. The data indicate that opioid peptides co-released with VP (like dynorphin) may be responsible for cross-inhibition of OT release during dehydration. This suggests that dynorphin acts in a paracrine way, making it a strong candidate for this role.
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PMID:Enhanced Neurohypophyseal Vasopressin Release is Associated with Increased Opioid Inhibition of Oxytocin Release. 1921 47


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