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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of vasopressin and tetradecanoyl phorbol acetate (TPA) on cytosolic free Ca2+ ([Ca2+]i) and insulin release in HIT-T15 beta-cells. Saturable binding of [3H] [Arg8]-vasopressin to HIT cell microsomes indicated a single class of receptors with a dissociation constant (Kd) of 2.5 nM and a total number of binding sites (Bmax) equal to 120 fmol/mg protein. [Arg8]-vasopressin (0.1-100 nM) elicited dose-dependent insulin release from HIT cells by up to 25-fold. This increase was dependent on the presence of extracellular glucose and was blocked by omission of extracellular Ca2+ or addition of verapamil. The stimulation was biphasic; a rapid but short-lived large increase in release was followed by a smaller sustained rise. Vasopressin also evoked a marked, concentration-dependent increase in [Ca2+]i which was also biphasic; an initial spike was followed by a sustained elevation. This increase also required glucose and was blocked by the absence of extracellular Ca2+ or the addition of verapamil. Pretreatment of the cells with TPA overnight to deplete protein kinase C activity did not affect the [Ca2+]i or insulin responses to vasopressin. However, short-term exposure to TPA markedly reduced glucose-induced steady-state [Ca2+]i, despite potentiating glucose-stimulated insulin release sevenfold, and blocked the [Ca2+]i increase induced by vasopressin. These inhibitory effects of TPA were absent in protein kinase C-depleted cells and were prevented by staurosporine. TPA had no significant effect on vasopressin-induced insulin release. Vasopressin did not modify the activity of ATP-sensitive K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of insulin release by vasopressin in the clonal beta-cell line, HIT-T15: the role of protein kinase C. 151 19

This review covers the recent developments gained in the exploration of V1-vascular vasopressin (AVP) receptors. We examine the different radioligands available for the pharmacological characterization of these receptors. The immediate transmembrane signaling of V1-vascular AVP receptors involves ligand-receptor complex formation, receptor lateral mobility and internalization, coupling to a Gq protein, activation of phospholipases A2, C and D, translocation and activation of protein kinase C, production of inositol 1,4,5-triphosphate and 1,2-diacylglycerol, mobilization of intracellular calcium, alteration of intracellular pH with activation of the Na+/H+ exchanger, calmodulin activation and myosin light chain phosphorylation. The secondary nuclear signal mechanisms triggered by activation of V1-vascular AVP receptors includes tyrosine phosphorylation, induction of gene expression and protein synthesis.
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PMID:Signal transduction of V1-vascular vasopressin receptors. 153 67

We have studied the effects of the vasoactive agents phorbol 12-myristate 13-acetate (PMA) and vasopressin (VP) on phosphatidylcholine metabolism in cultured rat glomerular mesangial cells. PMA and VP stimulate the incorporation of [3H]choline into phosphatidylcholine and the release of [3H]choline into the culture medium. VP, but not PMA, also increases the release of phosphorylcholine into the medium. This suggests that PMA specifically stimulates phospholipase D, whereas VP stimulates phospholipases C and D. Experiments were also conducted to look for production of phosphatidic acid and diacylglycerol, products of phospholipase D- and C-mediated breakdown of phosphatidylcholine. Treatment of cells prelabeled with [3H]myristic acid for 2.5 min with PMA or VP increases the content of [3H]myristic acid in diacylglycerol and phosphatidic acid. A dual labeling study ([3H]myristic acid and [14C]arachidonic acid) suggests that phosphatidylcholine is an important source of diacylglycerol in cells treated with VP and PMA. When PMA or VP are added to [3H]myristic acid-labeled cells in the presence of ethanol, increased labeling of phosphatidylethanol is seen as early as 2.5 min. Desensitization of protein kinase C by overnight treatment of cells with PMA blocked subsequent VP-stimulated formation of phosphatidylethanol and release of [3H]choline. When cells were simultaneously treated with VP and PMA, additive effects on phosphatidylethanol formation and [3H]choline release were observed.
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PMID:Vasopressin and phorbol ester-stimulated phosphatidylcholine metabolism in mesangial cells. 153 83

We have previously reported that vasopressin activates chloride channels, leading to depolarization of glomerular mesangial cells via both calcium-dependent and calcium-independent pathways (S.G. Kremer, W.V. Breuer, and K. L. Skorecki, J. Cell. Physiol. 138: 97-105, 1989). However, the calcium-independent pathways were not defined. Using fluorescent probes, we now demonstrate that activation of protein kinase C (PKC) results in cellular depolarization in the absence of a calcium signal. This depolarization is also mediated by an enhanced conductance to chloride. Downregulation of PKC partially attenuated but did not abolish the depolarization response to vasopressin. Depolarization persisted when, in addition, calcium responses were also abolished and prostaglandin production was eliminated, suggesting an additional pathway for depolarization. G protein activation by aluminum fluoride also resulted in cellular depolarization mediated by an enhanced conductance to chloride, which persisted when calcium and PKC-signaling pathways were eliminated. This suggests the presence of a calcium- and PKC-independent pathway for G protein-mediated chloride-dependent depolarization. These findings point to the presence of at least three separate signaling pathways available for the activation of mesangial cell chloride channels, i.e., calcium, PKC, and a G protein.
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PMID:Multiple signaling pathways for Cl(-)-dependent depolarization of mesangial cells: role of Ca2+, PKC, and G proteins. 156 80

Challenge of intact hepatocytes with one of the hormones vasopressin, angiotensin and glucagon or with the phorbol ester phorbol 12-myristate 13-acetate (PMA) led to a rapid increase in the activity of protein kinase C found in both cytosol and membrane fractions. Maximal activation by hormones occurred within 1-6 min of challenge of cells, after which activity declined. In membrane fractions protein kinase C activity return to basal levels some 15 min after exposure of cells to either angiotensin or glucagon. In cytosol fractions of cells challenged with hormones a second phase of activation ensued after about 10 min, with levels of protein kinase C activity remaining elevated above basal level 15 min afterwards. Activity changes elicited by PMA were rather different; it took about 15 min to achieve maximal activation of cytosolic protein kinase C activity. In membranes of cells challenged with PMA, an initial rapid and transient activation was followed by a sustained increase in activity occurring about 10 min after exposure of cells to this ligand. Only when hepatocytes were challenged with PMA was the translocation of protein kinase C from the cytosol to membrane fraction observed. The kinetics of PMA-induced translocation suggested that it accounted for the second phase of the increase in membrane protein kinase C activity which was unique to this ligand.
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PMID:Glucagon, vasopressin and angiotensin all elicit a rapid, transient increase in hepatocyte protein kinase C activity. 157 78

Increases in the intracellular Ca2+ concentration of human platelets caused by receptor agonists, such as thrombin, 9,11-epithio-11,12-methanothromboxane A2 (STA2), platelet-activating factor (PAF) and arginine-vasopressin, were inhibited by prior addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) in time-dependent and concentration-dependent manners. The inhibitions were mostly reversed by staurosporine, and inhibitor of protein kinase C, added 1 min before TPA. Prior treatment of platelets with thrombin or STA2, the efficacious Ca2+ mobilizer, suppressed the increase in the intracellular Ca2+ concentration of the cells to other agonists, but treatment with less efficacious PAF or vasopressin did not. The heterologous receptor desensitizations were also reversed by staurosporine. The antibody, directed against the carboxy-terminal region of the alpha subunits 1 and 2 of the inhibitory guanine-nucleotide-binding proteins (Gi1 alpha and Gi2 alpha), was raised in rabbit and was used to immunoprecipitate Gi alpha in 32P-labeled platelets. The radioactivity was detected in Gi alpha after incubation of 32P-labeled platelets with TPA, thrombin or STA2, but not in the cells incubated with PAF or vasopressin. The time-dependency or concentration-dependency of TPA-induced phosphorylation of Gi alpha was similar to the dependency of its inhibitory action on agonist-induced Ca2+ mobilization. Thus, strong activation of Ca2+/phospholipid-dependent protein kinase C by phorbol ester or agonists of certain Ca(2+)-mobilizing receptors leads to phosphorylation of the alpha subunit of guanine-nucleotide-binding protein, thereby impairing the coupling of the G protein to receptors as a feedback regulatory component of the receptor-triggered intracellular Ca(2+)-mobilizing system.
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PMID:Phosphorylation of the inhibitory guanine-nucleotide-binding protein as a possible mechanism of inhibition by protein kinase C of agonist-induced Ca2+ mobilization in human platelet. 157 85

Many hormones and drugs exert their effects on cells by increasing cytosolic Ca2+ (Cai2+) and activating protein kinase C (PKC). Each of these actions results in cholestasis in the isolated perfused rat liver, but the responsible mechanisms are unclear. We used isolated rat hepatocyte couplets to observe the direct effects of increased Cai2+ and PKC activation on permeability of the hepatocyte tight junction and canalicular volume, two possible determinants of hepatocyte bile secretion. Couplets were stimulated with the Ca2+ agonist vasopressin (10(-8) M) in the absence and presence of the Ca2+ influx antagonist Ni2+ (5 x 10(-3) M) or with the PKC activator phorbol dibutyrate (10(-6) M). Cai2+ was determined by ratio microspectrofluorometry of indo-1, permeability of the couplet tight junctions was assessed by exclusion of horseradish peroxidase from the canalicular space, and changes in canalicular volume over time were measured directly by optical planimetry. Canalicular volume increased by 1.6 +/- 2.5%/min (mean +/- SD) under basal conditions. In response to vasopressin, there was a rapid 15-fold increase in Cai2+, followed first by an increase in paracellular permeability, then by canalicular collapse (15.9 +/- 5.9%/min). Pretreatment with Ni2+ markedly decreased the vasopressin-induced increase in Cai2+ and abolished both the increase in paracellular permeability and the canalicular collapse. Phorbol dibutyrate also increased paracellular permeability but resulted in neither increased Cai2+ nor canalicular collapse. The PKC inhibitor H-7 reversed the effects of both vasopressin and phorbol dibutyrate on tight junction permeability. Bile secretory pressure, measured in isolated perfused rat liver preparations, was acutely increased by vasopressin, but the increase was augmented rather than inhibited by Ni2+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal regulation of paracellular permeability in isolated rat hepatocyte couplets. 161 38

Experiments were designed to characterize the hormone sensitive transport of Ca2+ from the external media into rat hepatocytes maintained in culture. In the absence of added vasopressin, hepatocytes were nearly impermeable to Ca2+, whereas a significant and rapid influx of Ca2+ could be detected when external Ca2+ was added to hepatocytes after the addition of 20 nM vasopressin. The transport was measured as the initial rate of increase of free intracellular Ca2+ [( Ca2+]i) after Ca2+ addition to the external media. Most data were obtained from the majority of cells on a coverslip immersed in a spectrophotometric cuvette, but selected data were obtained by measuring Ca2+ changes in single cells. Ca2+ influx measured using a large number of cells was similar to data obtained using single cells. The Vmax of Ca2+ influx was 140 nM/s. Ca2+ transport was competitive with H+ so that the Km was 17.4 mM at pH 6.8, 3.7 mM at pH 7.4 and 1.8 mM at pH 7.8. Ca2+ influx was insensitive to external K+ (1 to 70 mM) and to the presence of 5 nM valinomycin, suggesting that it was independent of the electrical potential gradient across the plasma membrane. Transport also appeared to be insensitive to the activity of protein kinase C, which was varied by addition of the activator, 12-myristate 13-acetate phorbol ester, and by addition of the kinase inhibitor, staurosporine. Stimulation of transport following vasopressin addition exhibited a delay with a t1/2 of approximately 30 s. A vasopressin antagonist blocked the activation of transport, if added prior to vasopressin. However, experiments designed to determine the effect of hormone occupancy per se on transport activity indicated that continued hormone occupancy was not required. When the external medium was nominally Ca2+ free and an antagonist was added 1 min after vasopressin, Ca2+ entry, even 8 min after antagonist addition, was rapid. Conversely, preincubation with vasopressin antagonist in medium containing 0.5 mM Ca2+ dramatically lowered plasma membrane Ca2+ permeability. The ER Ca2+ pool emptied by vasopressin was refilled in the presence of vasopressin antagonist plus 0.5 mM Ca2+, but did not refill when the medium contained no added Ca2+. Under the conditions of these experiments, the Ca2+ levels of the ER hormone-sensitive Ca2+ pool were estimated as well as intracellular concentrations of inositol-1,4,5-trisphosphate. The Ca2+ levels of the endoplasmic reticulum correlated inversely with plasma membrane Ca2+ permeability, whereas cellular concentrations of inositol-1,4,5-trisphosphate did not correlate with Ca2+ permeability.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of plasma membrane permeability to calcium in primary cultures of rat hepatocytes. 165 96

By using aortic adventitial fibroblasts in culture as a model, we first demonstrated that cells derived from spontaneously hypertensive rats (SHR), when compared with Wistar-Kyoto (WKY)-derived cells, possessed an increased capacity to proliferate and to synthesize DNA in response to vasoactive agents. At this early stage of culture, SHR fibroblasts exhibited a higher specific growth rate. Then, to gain insight into the mechanisms which could be responsible for the difference observed, signalling pathways involved in the transduction of the mitogenic signal were analysed in cells cultured for 3 days. Results indicated that, in SHR-derived fibroblasts, an increased phospholipase C activity could account for the higher mitogenic response to thrombin or vasopressin. However, this enzymatic activity, which did not differ when fibroblasts from the two rat strains were stimulated by serum, could not be responsible for the enhanced proliferation rate of SHR-derived cells. Moreover, neither protein kinase C nor pertussis toxin-sensitive G proteins appeared to contribute to the hyperresponsiveness exhibited by SHR fibroblasts. Our results indicate that the mechanism(s) responsible for such a difference vary according to the stimulus; they also suggest that adventitial fibroblasts may participate in the modified reactivity of vascular wall associated with hypertension.
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PMID:Increased proliferation of adventitial fibroblasts from spontaneously hypertensive rat aorta. 166 71

The present study examines the effect of reduction of protein kinase C (PKC) activity, as induced by either phorbol ester (PMA) down-regulation or staurosporine inhibition, on the secretion of ACTH from cultured anterior pituitary (AP) cells. Short-term (3 h) exposure of cells to 5 nM PMA resulted in almost complete desensitization to both PMA and vasopressin (AVP), while there was only a minor incidence on the effect of corticotropin-releasing factor (CRF). In contrast, long-term (12-24 h) exposure of cells to PMA, as well as pretreatment with staurosporine, dramatically reduced the stimulatory influence of CRF. This was shown not to be due to a decline in ACTH cells' stores, nor to the toxicity of phorbol ester or to a negative autofeedback of ACTH. Pretreatment of corticotrophs with PMA failed to dampen the CRF-induced cyclic AMP formation, while it caused a decline in the effects of forskolin and 8-bromoadenosine cyclic AMP. Stimulated ACTH secretion subsequent to either veratridine- or high K(+)-induced cell depolarization was likewise decreased. We conclude that in corticotrophs the stimulatory action of not only AVP, but also of that of CRF on ACTH secretion strongly relies on PKC activity. In the case of CRF, however, this may not be a primary consequence of receptor occupation, as evidence suggests an indirect relationship which may involve PKC regulation of Ca2+ channels and/or the ion's intracellular messenger function.
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PMID:Inhibition of protein kinase C activity in cultured pituitary cells attenuates both cyclic AMP-independent and -dependent secretion of ACTH. 166 63


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