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

The rate of vanadate-sensitive 22Na+ uptake by isolated liver membrane vesicles, reflecting transport by Na+/K(+)-ATPase, was measured to study the role played by phospholipase C and protein kinase C in the regulation of this process by vasopressin. Na+ uptake was enhanced 2-3-fold by 100 nM [Arg8]vasopressin and the hormone effect was mimicked by 0.1 microM inositol 1,4,5-trisphosphate as well as by 1.0 microM myo-inositol. The stimulation by vasopressin was potentiated by phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis (5-10 mU/ml). No effect of the bacterial enzyme was observed in the absence of the hormone. Phorbol myristate acetate (0.5-1 microM) suppressed the stimulation by vasopressin but had no effect in the absence of the hormone. High concentrations of bacterial phosphatidylinositol-specific phospholipase C (50-100 mU/ml) also antagonized the hormone stimulation. Staurosporine (50-100 nM) prevented the antagonistic effect of bacterial phospholipase C (50 mU/ml) and EGTA (1 mM) partially protected the hormonal stimulation in the presence of phorbol myristate acetate. Our results suggest that the stimulatory effect of vasopressin on Na+ transport is mediated by phospholipase C and products derived from the inositol moiety of membrane phospholipids. Membrane-associated protein kinase C appears to be at least partially responsible for the desensitization to stimulation by vasopressin.
 ...
PMID:Vasopressin stimulation of vanadate-sensitive Na+ transport by liver plasma membrane vesicles. Evidence for regulation via phospholipase C and protein kinase C activities. 139 Aug 61

The extracellular Ca2+ dependence of agonist stimulation of vascular smooth muscle (VSM) has been investigated in rat cultured aortic smooth muscle cells (SMCs) and isolated mesenteric resistance vessels (MRVs). Agonists such as [Arg8]vasopressin (AVP), angiotensin II (Ang II), and adenosine-5'-triphosphate (ATP) stimulated 45Ca2+ entry into the SMCs that was (a) independent of the extent to which the membranes were polarized, and (b) was not inhibited by organic Ca2+ channel antagonists. Measuring the intracellular Ca2+ concentration [( Ca2+]i) after stimulation with agonists revealed a rapid increase of [Ca2+]i, which was followed by a sustained rise that was insensitive to Ca2+ antagonists. In Ca2+-free medium, only the initial peak of [Ca2+]i was still observed, but the sustained response to the agonists disappeared completely. This observation indicates that the sustained elevation seen in Ca2+-containing medium was the consequence of agonist-induced Ca2+ entry. In MRVs, a corresponding Ca2+-antagonist-insensitive, agonist (norepinephrine and AVP)-induced tonic tension was also identified. Moreover, agonists were able to induce sustained tension in the MRVs regardless of whether the membrane was normally polarized or was previously depolarized (80 mM K+) upon their administration. The agonist-stimulated 45Ca2+ entry in the SMCs could be blocked by the multivalent cations La3+, Cd2+, Mn2+, Co2+, Ni2+, and Mg2+ (in this order of potency). Depolarization-induced 45Ca2+ influx was inhibited by these cations in the same order of potency, but was significantly more sensitive to Cd2+ and significantly less sensitive to La3+ than that stimulated by agonists. Treatment with 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate (NCDC, a proposed inhibitor of phospholipase C) reduced both the agonist-induced 45Ca2+ influx and the sustained elevation of [Ca2+]i in the SMCs. NCDC also abolished both contraction and depolarization induced by agonists in the MRVs. The kinase C stimulator phorbol-12-myristate-13-acetate (PMA) inhibited the agonist-induced 45Ca2+ influx and sustained increase in [Ca2+]i in the SMCs, whereas the kinase C inhibitor staurosporine had no effect. In the MRVs, in contrast, PMA had no influence on agonist-induced contractions. Staurosporine (1 microM), however, completely prevented these contractions, as did NCDC, but, unlike NCDC, it did so without affecting the agonist-induced depolarization. These data support an important role of receptor-operated Ca2+-permeable channels in VSM activation by agonists and suggest that these channels may be controlled by intracellular enzymic pathways and second messenger systems.
 ...
PMID:Receptor-operated calcium-permeable channels in vascular smooth muscle. 247 25

In the present study, we examined the effect of vasopressin (AVP) on phosphatidylcholine-hydrolyzing phospholipase D activity in primary cultured rat aortic smooth muscle cells. AVP stimulation of choline formation was dose dependent. The time-course was quite different from those of inositol phosphates. The effect of AVP on the formation of inositol phosphates (EC50 was 3 nM) was more potent than that on the formation of choline (EC50 was 30 nM). 12-O-Tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC), stimulated the formation of choline. However, 4 alpha-phorbol 12,13-didecanoate, which is inactive for PKC, had little effect. Staurosporine, an inhibitor of protein kinases, which inhibited the TPA-induced formation of choline, had little effect on the AVP-induced formation of choline. Neither calphostin C, a highly specific PKC inhibitor, nor PKC down-regulation with TPA affected AVP-induced formation of choline. A combination of AVP and TPA additively stimulated the formation of choline. The depletion of extracellular Ca2+ by (ethylenebis(oxyethylenenitrilo)tetraacetic acid significantly reduced the AVP-induced formation of choline. W-7, an antagonist of calmodulin, inhibited the AVP-induced formation of choline in a dose-dependent manner. NaF, an activator for GTP-binding protein (G-protein), stimulated the formation of choline. However, the formation of choline by a combination of AVP and NaF was not additive. Pertussis toxin had little effect on the AVP-induced formation of choline.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vasopressin activates phospholipase D through pertussis toxin-insensitive GTP-binding protein in aortic smooth muscle cells: function of Ca2+/calmodulin. 757 93

In the rat medullary thick ascending limb (MTAL), hyperosmolality inhibits transepithelial HCO3- absorption (JHCO3-) by inhibiting apical membrane Na+/H+ exchange. To examine signaling mechanisms involved in this regulatory response, MTALs were isolated and perfused in vitro with 25 mM HCO3- solutions (290 mosmol/kg H2O). Osmolality was increased in lumen and bath solutions by addition of 300 mM mannitol or 75 mM NaCl. Addition of mannitol reduced JHCO3- by 60% and addition of NaCl reduced JHCO3- by 50%. With the protein tyrosine kinase (PTK) inhibitor genistein (7 microM) or herbimycin A (1 microM) in the bath, addition of mannitol reduced JHCO3- only by 11% and addition of NaCl reduced JHCO3- only by 15%. Staurosporine (10(-7) M) or forskolin (10(-6) M) in the bath had no effect on inhibition of JHCO3- by hypertonic NaCl. Genistein had no effect on inhibition of JHCO3- by vasopressin (a cyclic AMP-dependent process) or stimulation of JHCO3- by prostaglandin E2 (a protein kinase C-dependent process). Under isosmotic conditions, addition of genistein or herbimycin A to the bath increased JHCO3- by 30% through stimulation of apical membrane Na+/H+ exchange. Addition of the tyrosine phosphatase inhibitor molybdate (50 microM) to the bath reproduced the inhibition of JHCO3- observed with hyperosmolality. These data indicate that 1) the effect of hyperosmolality to inhibit MTAL HCO3- absorption through inhibition of apical membrane Na+/H+ exchange is mediated via a PTK-dependent pathway that functions independent of regulation by cyclic AMP and protein kinase C, and 2) a constitutive PTK activity inhibits apical membrane Na+/H+ exchange and HCO3- absorption under isosmotic conditions. Our results suggest that tyrosine phosphorylation is a critical step in inhibition of the apical Na+/H+ exchanger isoform NHE-3 by hyperosmolality.
 ...
PMID:Hyperosmolality inhibits bicarbonate absorption in rat medullary thick ascending limb via a protein-tyrosine kinase-dependent pathway. 773 Mar 71

The effects of the protein kinase C inhibitors staurosporine and H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine] on glucose-induced regulation of glycogen synthase and phosphorylase activities were investigated in the primary culture of hepatocytes. Glycogen synthesis as measured by the incorporation of [14C]glucose into glycogen was enhanced up to 78% (P < .001) by 100 nmol/L staurosporine. In contrast, H-7 inhibited glycogen synthesis in a dose-dependent manner, with an IC50 value of 70 mumol/L. Activation of glycogen synthase by 30 mmol/L glucose was enhanced significantly (P < .02 and less) by staurosporine at 20 nmol/L and higher concentrations whereas the activity of this enzyme was inhibited by H-7 (IC50 = 50 mumol/L). The inactivation of phosphorylase by glucose was significantly greater when staurosporine was included in the medium. However, H-7 increased the phosphorylase activity ratio by 1.5- to 2.5-fold at concentrations of 20 to 100 mumol/L. The time course of synthase activation and phosphorylase inactivation showed that the effect of glucose was enhanced by staurosporine and inhibited by H-7. These novel reciprocal effects of protein kinase C inhibitors were also observed at different concentrations of glucose. The effects of H-8, a compound with structural resemblance to H-7 and an inhibitor of protein kinase A, were similar to those of staurosporine but not to those of H-7. Staurosporine blocked the effects of vasopressin and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), whereas H-7 in combination with these protein kinase C activators acted in the same direction. The effects of staurosporine, a relatively more specific inhibitor of protein kinase C, indicated that this enzyme plays a role in the regulation of glycogen metabolism in liver. However, H-7, which is known to have protein kinase C-independent effects in intact cells, seems to alter the activities of glycogen synthase and phosphorylase by a different mechanism.
 ...
PMID:Reciprocal effects of the protein kinase C inhibitors staurosporine and H-7 on the regulation of glycogen synthase and phosphorylase in the primary culture of hepatocytes. 823 44

A mechanism by which vasopressin enhances phospholipase A2 activation in rabbit platelets was investigated. Stimulation of the platelets with vasopressin enhanced arachidonic acid liberation, as well as aggregation and ATP secretion in the presence of submaximal concentration of A23187, although vasopressin alone had no effect. The vasopressin-enhanced liberation was inhibited by p-bromophenacyl bromide, a phospholipase A2 inhibitor, and by genistein, a tyrosine kinase inhibitor. Though epinephrine also caused a similar enhancement of the liberation, this effect of epinephrine was insensitive to genistein. Staurosporine, a protein kinase C inhibitor, completely suppressed phorbol 12-myristate 13-acetate-enhanced arachidonic acid liberation, but suppressed the vasopressin-induced enhancement only slightly. These results suggest that vasopressin-enhanced phospholipase A2 activation may be regulated by a genistein-sensitive mechanism, most likely by a protein tyrosine kinase-mediated pathway, but not by guanine nucleotide-binding protein- or protein kinase C-mediated pathway.
 ...
PMID:Enhancement of A23187-induced arachidonic acid liberation by vasopressin is sensitive to genistein in rabbit platelets. 826 Sep 37

Vasopressin stimulated GSH efflux from Hep G2 cells. The maximal effect was observed at 10nM. Pretreatment with pertussis toxin or cholera toxin for 18 hr increased GSH efflux. Vasopressin-mediated GSH efflux was observed even in the cells pretreated with those compounds. Dibutyryl-cAMP or dibutyryl-cGMP enhanced GSH efflux although an additive effect of vasopressin was not observed. Glucagon and a phorbol ester independently increased GSH efflux while both compounds decreased the effect of vasopressin. Staurosporine, an inhibitor of protein kinase C, inhibited vasopressin-mediated GSH efflux. The effect of vasopressin was observed even in the absence of extracellular Ca2+. Vasopressin stimulates GSH efflux from Hep G2 cells and protein kinase C-dependent pathway may play a significant role in vasopressin-mediated GSH efflux.
 ...
PMID:Characterization of vasopressin-mediated GSH efflux from Hep G2 cells: significance of protein kinase C. 845 Jul 14

Incubation of the toad bladder epithelia with 100 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) for 1, 3 and 5 min decreased cytosolic protein kinase C (PKC) activity to 85, 80 and 75% of control, while membrane-associated PKC activity increased to 127, 140 and 126% of control, respectively. Long-term treatment of epithelial cells with TPA caused downregulation of PKC with a loss of 80% of the enzymic activity. Incubation with vasopressin (AVP) for 2 min decreased cytosolic PKC activity by 20%, whereas the activity in the membrane fraction increased by 33%. PKC translocation did not occur when epithelia were stimulated with [deamino1-D-arginine8]-vasopressin which binds more specifically to the V2 receptor. Staurosporine inhibited PKC activity as well as the effect of AVP on translocation. Phorbol esters decreased the response to AVP on water transport, whereas staurosporine greatly increased the hormonal response. We conclude that TPA induces an intracellular translocation and downregulation of PKC. The translocation of PKC by AVP and the inhibition of AVP-stimulated water flow by TPA suggest a significant negative feedback loop involving PKC to modulate the action of AVP.
 ...
PMID:Vasopressin stimulates translocation of protein kinase C in the toad urinary bladder. 877 78

Noradrenaline increased phosphorylase a activity through activation of alpha1B-adrenoceptors in rat hepatocytes. Such effect was inhibited by chloroquine (Ki approximately 55 nM) and only slightly reduced by high concentrations of primaquine. Chloroquine did not inhibit the activation of phosphorylase a induced by vasopressin or angiotensin II. Binding competition experiments using [3H]prazosin showed that both chloroquine and primaquine interact with alpha1B-adrenoceptors, but only at very high concentrations. This indicates that the ability of chloroquine to block the alpha1B-adrenergic action was not due to antagonism at the receptor level. Noradrenaline increased phosphatidylinositol resynthesis and inositol trisphosphate production; these effects were inhibited by chloroquine and phorbol 12-myristate 13-acetate. Staurosporine and Ro 31-8220 (3-[1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3 -yl)maleimide), reduced the inhibitions induced by the active phorbol ester and the antimalarial drug on adrenergic-stimulated phosphatidylinositol resynthesis. Similarly, staurosporine blocked the inhibitory actions of chloroquine and phorbol 12-myristate 13-acetate on noradrenaline-stimulated inositol trisphosphate production. These data suggest the possibility that protein kinases, such as protein kinase C, could be involved in the actions of chloroquine.
 ...
PMID:Chloroquine inhibits alpha1B-adrenergic action in hepatocytes. 954 5

In the present study, we examined the effect of vasopressin on the induction of the low-molecular-weight heat shock proteins heat shock protein 27 (HSP27) and alphaB-crystallin in an aortic smooth muscle cell line, A10 cells. Vasopressin induced a time-dependent accumulation of HSP27 and alphaB-crystallin. The stimulatory effects of vasopressin were dose-dependent over the range 0.1 nmol/L to 0.1 micromol/L. The EC50 values for vasopressin were 2 (HSP27) and 4 nmol/L (alphaB-crystallin). Vasopressin induced increases in the levels of the mRNAs for HSP27 and alphaB-crystallin. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, induced an accumulation of HSP27 (EC50, 20 nmol/L) and alphaB-crystallin (EC50, 2 nmol/L). In contrast, 4alpha-phorbol 12,13-didecanoate, a non-PKC-activating phorbol ester, had no such effect. Staurosporine and calphostin C, inhibitors of PKC, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin as well as that induced by TPA. BAPTA/AM and TMB-8, inhibitors of intracellular Ca2+ mobilization, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin. These results strongly suggest that vasopressin stimulates the induction of HSP27 and alphaB-crystallin via PKC activation in vascular smooth muscle cells and that this effect of vasopressin is dependent on intracellular Ca2+ mobilization.
 ...
PMID:Vasopressin stimulates the induction of heat shock protein 27 and alphaB-crystallin via protein kinase C activation in vascular smooth muscle cells. 992 48


1