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)

Angiotensin II, catecholamines, and vasopressin can stimulate the phosphorylation of 10 hepatic cytosolic proteins via a Ca2+-linked, cyclic AMP-independent mechanism. To explore the role of known Ca2+-sensitive protein kinases in this response, [32P]PO4(3-)-labeled hepatocytes were stimulated with various agonists, the cytoplasmic proteins were separated on two-dimensional gels, and the resulting autoradiographs were computer analyzed. The role of phosphorylase kinase was examined using hepatocytes from gsd/gsd rats which are deficient in this enzyme. The phosphorylation state of phosphorylase was not increased by glucagon, angiotensin II, or vasopressin in hepatocytes from the gsd/gsd animals. The phosphorylation state of all other substrates was changed by glucagon or the Ca2+-linked hormones to the same extent in gsd/gsd hepatocytes as in normal Wistar controls, suggesting that phosphorylase kinase plays a restricted role in the hormone response. The role of the Ca2+- and phospholipid-sensitive protein kinase (protein kinase C) was examined by stimulating hepatocytes with phorbol esters which are thought to activate protein kinase C by substituting for diacylglycerol. Phorbol esters increased the phosphorylation state of 3 of the 10 substrates affected by angiotensin II or vasopressin, but did not stimulate Ca2+ fluxes in hepatocytes. Treatment of hepatocytes with the Ca2+ ionophore A23187 mimicked the effect of the Ca2+-linked hormones on the phosphorylation of the other 7 substrates. The results demonstrate that at least three Ca2+-sensitive protein kinases are involved in the response of hepatocytes to Ca2+-linked hormones. Since these kinases can be activated independently by phorbol esters or A23187, the results imply that hormones such as vasopressin generate two intracellular messengers, diacylglycerol and Ca2+ ion.
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PMID:Evidence for the role of phosphorylase kinase, protein kinase C, and other Ca2+-sensitive protein kinases in the response of hepatocytes to angiotensin II and vasopressin. 623 Mar 57

Tumor promoting phorbol esters can stimulate Ca++-phospholipid-dependent protein kinase. It has been suggested that this enzyme may mediate the effects of calcium-dependent hormones. In this paper the effects of phorbol 12-myristate 13-acetate (TPA) on isolated rat hepatocyte metabolism were studied. Phorbol esters completely blocked alpha 1-adrenergic stimulation of glycogenolysis. This effect is quite specific for alpha 1-adrenergic actions, as the stimulations of glycogenolysis by vasopressin, angiotensin II, ionophore A-23187 and glucagon were unaffected by TPA. The potencies of the different phorbol esters used in this study suggests that the inhibitory effects of these agents may be due to activation of protein kinase C. The effect of phorbol esters on alpha 1-adrenergic actions seems to occur at an early step of the alpha 1-adrenergic action. TPA (10(-11) -10(-6)M) was unable to stimulate glycogenolysis. Urea synthesis, which is stimulated by vasopressin and alpha 1-adrenergic agents, was not stimulated by phorbol ester, neither alone nor in combination with the Ca++ ionophore A-23187.
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PMID:Phorbol esters inhibit alpha 1 adrenergic stimulation of glycogenolysis in isolated rat hepatocytes. 632 79

Utilizing [3H]phorbol dibutyrate [P(Bu)2], we have developed an assay for high-affinity phorbol ester receptors in intact rat embryo fibroblasts. At 37 degrees C, binding of [3H]P(Bu)2 reached a maximum within 10 min and was rapidly reversible. The tumor promoters 12-O-tetradecanoyl-phorbol 13-acetate, teleocidin B, and mezerein were potent inhibitors of [3H]P(Bu)2 binding. Phorbol and 4-alpha-phorbol didecanoate, which lack tumor-promoting activity, did not inhibit [3H]P(Bu)2 binding. Epidermal growth factor, platelet-derived growth factor, fibroblast growth factor, arginine and lysine vasopressin, luteinizing-hormone releasing hormone, and diazepam did not inhibit [3H]P(Bu)2 binding. A Scatchard analysis was compatible with two classes of binding sites, one with Kd = 8 nM and about 1--2 x 10(5) sites per cell and the other with Kd = 710 nM and about 3 x 10(6) sites per cell. Sera from various species, human amniotic fluid, and certain tissue extracts inhibited specific binding of [3H]P(Bu)2. Fractionation of human serum led to 135-fold purification of an inhibitory factor with a molecular weight in the range 40,000 to 80,000.
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PMID:Identification of receptors for phorbol ester tumor promoters in intact mammalian cells and of an inhibitor of receptor binding in biologic fluids. 694 Dec 90

It has been reported that glucocorticoid modifies phosphoinositide (PI) hydrolysis stimulated by vasoactive agents in vascular smooth muscle cells. In the present study, we investigated the point at which glucocorticoid affects vasopressin-induced PI hydrolysis in primary cultured rat aortic smooth muscle cells. The pretreatment with dexamethasone significantly amplified the formation of inositol trisphosphate (IP3) induced by vasopressin in a dose-dependent manner in a range of 1 pM to 10 nM. The effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone had little effect on the number of vasopressin receptor and its affinity to vasopressin. The pretreatment with dexamethasone also amplified the formation of IP3 induced by NaF, a GTP-binding protein activator, or angiotensin II. 12-O-Tetradecanoylphorbol-13-acetate, a protein kinase C (PKC)-activating phorbol ester, significantly reduced the dexamethasone-induced enhancement of IP3 formation stimulated by vasopressin, angiotensin II or NaF 4 alpha-Phorbol-12, 13-didecanoate, a PKC-nonactivating phorbol ester, had little effect on the enhancement by dexamethasone. These results strongly suggest that glucocorticoid amplifies vasopressin-induced PI hydrolysis at a point downstream from GTP-binding protein in primary cultured rat aortic smooth muscle cells, and that the activation of PKC has a negative feedback effect on the amplification by glucocorticoid of vasopressin-induced PI hydrolysis.
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PMID:Glucocorticoid amplifies vasopressin-induced phosphoinositide hydrolysis in aortic smooth muscle cells. 776 86

Phospholipase D (PLD) is activated in mammalian cells in response to a wide variety of stimuli. A rapid assay for agonist-activated PLD activity in cell extracts was developed, utilizing a fluorescent derivative of phosphatidylcholine as substrate. Utilization of the substrate was assessed following thin-layer chromatography of the reaction mixture. Hydrolysis products generated by phospholipases D, C, and A2 could be visualized in the same reaction. Phorbol ester and vasopressin increased PLD activity in intact A7r5 vascular smooth muscle cells, as measured by an isotopic labeling method. Using the in vitro fluorescent assay, enhanced PLD activity was detected in membranes prepared from A7r5 cells that had been treated with phorbol ester or vasopressin. The agonist-activated activity was independent of phosphorylation occurring during the course of the assay. PLD activity was detected, in varying amounts, in membranes prepared from a variety of different mouse tissues. These results show that a fluorescent assay can be used to rapidly assess the activity of PLD and other phosphatidylcholine-utilizing phospholipases in cell and tissue extracts. The effects of agonists on PLD activity can be retained and quantitated in a broken cell preparation, permitting characterization of the agonist-activated form of the enzyme.
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PMID:A fluorescent assay for agonist-activated phospholipase D in mammalian cell extracts. 805 46

To define the role of protein kinase C (PKC) in oxygen-dependent production of erythropoietin (EPO) in the liver, we have determined EPO messenger ribonucleic acid (mRNA) expression in primary cultures of juvenile rat hepatocytes incubated at different oxygen tensions in the absence and presence of phorbol esters, vasopressin, and structurally different kinase inhibitors. Upon reduction of oxygen concentrations from 40% to 3% EPO mRNA in cultured hepatocytes increased markedly within 1.25 h, reached maximal values after 2.5 h and remained elevated for up to 72 h. Treatment of hepatocytes during 1.25-5 h of hypoxic exposure with phorbol 12-myristate-13 acetate (PMA) attenuated hypoxia-induced EPO mRNA levels dose-dependently by a maximum of approximately 50%. This inhibitory effect of PMA disappeared upon treatment for more than 5 h and was completely lost after incubation for 9 and 18 h in the presence of 10(-6) M and 10(-7) M PMA, respectively. Phorbol 12,13-dibutyrate and vasopressin also inhibited EPO mRNA accumulation, whereas 4 alpha-phorbol 12,13-didecanoate was ineffective. Western blot analysis of PKC isozymes revealed the presence of PKC alpha, beta II, delta, epsilon and zeta and provided no evidence that the PMA-induced inhibition of EPO expression was associated with depletion of any of these isozymes. Conversely, PMA-induced inhibition of EPO mRNA accumulation was paralleled by translocation of PKC alpha from cytosol to membranes and the time- and dose-dependent attenuation of the inhibitory effect of PMA on EPO mRNA levels was paralleled by down-regulation of PKC alpha. A dose-dependent inhibition of EPO mRNA formation, independent of effects on total RNA synthesis, as determined by [3H]uridine incorporation, was also found in the presence of the kinase inhibitor staurosporine (ED50 approximately 2 x 10(-8) M) and three structurally related derivatives with increased selectivity for PKC (RO 317549, ED50 approximately 1 x 10(-6) M; RO 318220, ED50 approximately 1 x 10(-6) M and CGP 41251, ED50 approximately 4 x 10(-6) M). The markedly lower potency of the latter three compounds as compared to staurosporine suggests that this suppression of EPO gene induction was not mediated by inhibition of PKC. In summary the data indicate that PKC alpha is a negative modulator of EPO gene expression in hepatocytes. A kinase other than PKC, however, appears to be an essential element of hypoxic signalling.
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PMID:Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C. 814 21

Addition of endothelin-1 or endothelin-3 to rat renal papillary tubules produced a dose-dependent inhibition of the cAMP response to vasopressin stimulation. The average EC50 values were 1.1 +/- 0.6 and 2.6 +/- 1.1 nM, respectively, indicating mediation by an endothelin ETB receptor. Phorbol myristate acetate (1 microM) also inhibited the vasopressin-cAMP response and this inhibition was not additive with that to endothelin, indicating that the endothelin inhibition is mediated by activation of protein kinase C. These findings demonstrate functionally relevant endothelin ETB receptors on renal papillary tubules. Such receptors are a possible target for endothelin-3 produced within the kidney.
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PMID:Functional endothelin ETB receptors on renal papillary tubules. 825 66

We have identified immunologically the protein kinase C (PKC) isoforms present in rat mesenteric small arteries, defined their distribution between particulate and soluble fractions, and studied their involvement in phorbol ester-induced contraction. Our analysis revealed the presence of the CA(2+)-dependent PKCs (alpha and gamma), Ca(2+)-independent PKCs (delta and epsilon), and the atypical isoform (zeta). PKCbeta could not be detected, whereas PKCgamma is likely to be of neural origin. All isoforms exhibited different distributions. PKCalpha, PKCepsilon, and PKCzeta were found in both particulate and soluble fractions. In contrast, PKCdelta was mainly in the particulate fraction, and PKCgamma was in the soluble fraction. Phorbol esters, which activate PKC and cause smooth muscle contraction, downregulated only the alpha and delta isoforms. This was associated with a parallel loss of contractile response to phorbol ester. The force developed to submaximal concentrations of noradrenaline was decreased after phorbol dibutyrate pretreatment, although the sensitivity and maximal response were unchanged. Phorbol ester pretreatment did not affect the contractile response to vasopressin. The sensitivity to non-receptor-mediated contraction, caused by k+ in the presence of prazosin, was slightly reduced by 4 alpha- and 4 beta-phorbol ester pretreatment. Maximal tension in response to this agonist was not affected. We conclude that PKCalpha and/or PKCdelta is necessary for phorbol ester-mediated contraction but is not essential for noradrenaline-, vasopressin-, or k(+)-induced contraction, demonstrating differences in the mechanisms involved in the contractile response between these agents.
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PMID:Identification of protein kinase C isoforms in rat mesenteric small arteries and their possible role in agonist-induced contraction. 862 Jun

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.
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PMID:Vasopressin stimulates translocation of protein kinase C in the toad urinary bladder. 877 78

Treatment of quiescent Swiss 3T3 cells with bombesin induces a rapid (</=40 s) and transient increase in the kinase activity of the Src family of tyrosine kinases, as determined by autophosphorylation in immune complex kinase assays (4.6 +/- 0.2-fold stimulation, n = 44) and phosphorylation of exogenous substrates. Phorbol 12, 13-dibutyrate increased the activity of Src family kinases with similar kinetics but was less effective than bombesin. However, Src family kinase activation by bombesin is not dependent either on protein kinase C or Ca2+. Bombesin stimulation of Src family kinase activity could also be dissociated from p125 focal adhesion kinase tyrosine phosphorylation. Neither treatment with cytochalasin D nor placement of the cells in suspension prevented the stimulation of Src family kinase activity induced by bombesin, but both abolished bombesin-induced tyrosine phosphorylation of p125 focal adhesion kinase. The stimulation of the Src family kinase activity by bombesin was completely prevented by treatment with vanadate, a potent inhibitor of protein-tyrosine phosphatases. Bradykinin and vasopressin also stimulated Src family kinase activity transiently, and this stimulation was also inhibited by vanadate. Our results dissect two separate pathways that lead to protein tyrosine phosphorylation in neuropeptide-stimulated Swiss 3T3 cells.
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PMID:Bombesin, bradykinin, vasopressin, and phorbol esters rapidly and transiently activate Src family tyrosine kinases in Swiss 3T3 cells. Dissociation from tyrosine phosphorylation of p125 focal adhesion kinase. 891 Mar 89


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