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)

Ca2+-mobilizing receptor-induced inositol phospholipid hydrolysis has been studied in cultured endothelial cells (EC) from human aorta, pulmonary artery, and umbilical vein. It was shown that in EC the release of inositol phosphates can be stimulated by histamine, thrombin, serotonin, acetylcholine, carbachol, bradykinin, vasopressin, angiotensin II, platelet-activating factor (PAF), the thromboxane A2 mimetic, U46619, and prostaglandin E2. The most effective agonists were thrombin, histamine, and PAF, producing two- to five-fold increases in inositol phosphate level, and a 50-90% elevation of the level of inositol trisphosphate within 5 min. Effects of other agonists were smaller, although significant. Incubation of EC with histamine or PAF for 1 h resulted in a four- to eight-fold decrease of beta-adrenoreceptor density in the plasma membranes. The activity of isoproterenol-stimulated adenylate cyclase was depressed, and the degree of stimulation by isoproterenol was reduced. Similar effects were obtained after treatment of EC with the protein kinase C activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, suggesting a role of protein kinase C in receptor desensitization. It is concluded, that stimulation of inositol phospholipid hydrolysis, and, consequently, activation of protein kinase can cause receptor imbalance in human vascular endothelium. This mechanism may play a pivotal role in the pathogenesis of cardiovascular and pulmonary diseases.
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PMID:Regulation of phosphoinositide turnover in endothelium from human pulmonary artery, aorta and umbilical vein. Antagonistic action on the beta-adrenoceptor coupled adenylate cyclase system. 254 21

Endothelium-dependent vasodilators, nitrates, and atrial natriuretic factor relax blood vessels by increasing vascular cyclic guanosine monophosphate (cGMP). The mechanisms by which cGMP relaxes vascular smooth muscle (VSM) are not known. Since contraction of VSM is associated with increased intracellular calcium and pH, we hypothesized that cGMP may decrease vascular tone by lowering ionized, intracellular calcium [( Ca2+]i) and pH. We used microfluorometry to measure cGMP-induced changes in intracellular calcium and pH of cultured A7r5 VSM cells after stimulation with contractile agonists. A cGMP analogue, 8-Br-cGMP, blocked vasopressin- but not thrombin-stimulated increases in [Ca2+]i. High extracellular potassium concentrations [( K+]) increased [Ca2+]i, but the attenuation of [Ca2+]i by 8-Br-cGMP was not statistically significant. 8-Br-cGMP also attenuated vasopressin- but not thrombin-stimulated alkalinization of VSM cells. cGMP may decrease vascular tone by decreasing [Ca2+]i and pH, but these changes are dependent on the contractile agonist studied.
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PMID:Effect of 8-bromo-cyclic guanosine monophosphate on intracellular pH and calcium in vascular smooth muscle. 254 26

The effect of calcium ions on the lipoprotein lipase (LPL) activity in rat adipocytes has been investigated. Incubation of the cells in the absence of extracellular calcium produced a rapid decline of LPL activity in the cells. The enzyme, however, could be immediately reactivated in less than 3 min by the addition of calcium. The degree of reactivation was proportional to the concentration of extracellular calcium. alpha 1 agonists phenylephrine and methoxamine affected LPL activity only slightly, as did vasopressin and angiotensin II. In contrast, calcium ionophore A23187 elicited a quick and transient enzyme activation which reached its peak 4 min after the addition of the drug. Thrombin (0.1 U/ml) produced the most rapid and intense response. The effect of thrombin was already evident 10 s after its addition, and the enzyme activity almost doubled above the basal level. Extracellular calcium was necessary to achieve thrombin activation. Contrary to previous thought, these data support the conclusion that LPL may undergo rapid activation, and that calcium ions are critically involved in this activation process. Thrombin rapidly raises LPL activity and may be one of its physiological activators in vivo.
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PMID:Rapid modulation of rat adipocyte lipoprotein lipase: effect of calcium, A23187 ionophore, and thrombin. 254 63

Incubation of cultured rat aortic smooth muscle cells (A-10, ATCC CRL 1476) with [8-arginine]vasopressin (AVP) or thrombin increased the amount of DNA strand breakage induced by camptothecin, an inhibitor of topoisomerase I (DNA topoisomerase; EC 5.99.1.2) and transiently stimulated the extractable activity of this enzyme. Both topoisomerase-related responses were prevented by treatment of the cells with AVP or thrombin plus the appropriate receptor antagonist. The increase in strand breakage mediated by AVP and thrombin depended on the concentration of hormone. Neither AVP nor thrombin had any effect on strand breaks obtained with the epipodophyllotoxin VM-26, an inhibitor of topoisomerase II [DNA topoisomerase (ATP-hydrolysing); EC 5.99.1.3]. Pretreatment of the cells with pertussis toxin partially inhibited thrombin-mediated increases in camptothecin-induced strand breakage whereas AVP-mediated increases were unaffected. These results are consistent with the notion that AVP and thrombin induce a transient increase in intracellular topoisomerase I activity via interactions with their respective cell surface receptors and that the effects of the activation of these receptors are mediated by different G-proteins.
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PMID:Stimulation of intracellular topoisomerase I activity by vasopressin and thrombin. Differential regulation by pertussis toxin. 255 99

To elucidate the cellular mechanism by which endothelin (ET) is secreted, we have studied the effects of a variety of vasoactive agents on the secretion of immunoreactive (IR)-ET from cultured bovine endothelial cells (EC). Confluent bovine EC cultured in serum-free medium secreted IR-ET as a function of time. Not only thrombin, but also vasoconstrictive hormones, such as arginine-vasopressin (AVP) and angiotensin (ANG) II, dose-dependently stimulated IR-ET secretion, and these effects were completely abolished by V1-receptor antagonist and [Sar1,Ala8]-ANG II, respectively. Protein kinase C (PKC)-activating phorbol ester and Ca2+ ionophore ionomycin had stimulatory effects on IR-ET secretion, and the combination of both compounds had a synergistic effect. These data suggest that AVP and ANG II, like thrombin, stimulate ET secretion from EC by a mechanism possibly involving receptor-mediated mobilization of intracellular Ca2+ and activation of PKC.
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PMID:Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells. 265 22

We have developed an ion-pair reverse-phase HPLC method to measure inositol phosphates in 32P-labeled cells. The different chromatographic parameters were analyzed to optimize the resolution of the 32P-labeled metabolites. Analysis of inositol phosphates in biological samples was improved by a single charcoal pretreatment which eliminated interfering nucleotides without removing inositol phosphates. The kinetics of production of inositol phosphates in calcium-activated erythrocytes, vasopressin-stimulated hepatocytes, and thrombin-activated platelets were analyzed. Original data on the activation of phosphoinositide phospholipase C were obtained in intact erythrocytes by direct measurement of inositol (1,4,5)P3. Data from agonist-stimulated hepatocytes and platelets were consistent with those from previous studies. In conclusion, this technique offers many advantages over the methodologies currently employed involving anion-exchange chromatography and [3H]inositol labeling: (i) 32P labeling is less expensive and more efficient than 3H labeling and can be used with all types of cells without permeabilization treatments and (ii) ion-pair HPLC gives good resolution of inositol phosphates from nucleotides with shorter retention times, and long reequilibration periods are not required.
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PMID:The separation of [32P]inositol phosphates by ion-pair chromatography: optimization of the method and biological applications. 275 4

Canine coronary resistance vessels were studied in vitro to examine the role of the endothelium in modulating responses to acetylcholine, vasopressin, and thrombin and to compare these responses to those found in large epicardial vessels. Acetylcholine had no effect on passively distended microvessels; however, after preconstriction with the thromboxane analogue, U 46619 caused dose-dependent vasodilation [50% effective concentration (EC50), 0.05 microM; maximum response, 97.9 +/- 2.1% relaxation]. Large epicardial arterial rings studied in organ chambers similarly relaxed to acetylcholine (EC50, 0.07 microM; maximum response, 79 +/- 5% relaxation). Hemoglobin was utilized to inactivate endothelium-derived relaxing factor (EDRF), resulting in reversal of acetylcholine vasodilation in both the microvessels (92 +/- 3.2% reversal) and the large epicardial vessels (117 +/- 9%). Hemoglobin had no effect on passively distended or preconstricted microvessels. Vasopressin constricted resistance vessels by 22.3 +/- 5.9 microns at 500 microU/ml. Hemoglobin potentiated this response by 100%, suggesting that vasopressin elicited EDRF release. In large coronary arteries, however, vasopressin elicited endothelium-dependent dilation with maximal relaxation of 36 +/- 9% at 3,000 microU/ml. Thrombin produced endothelium-dependent relaxation of large epicardial arterial rings but only constricted coronary microvessels. The response to thrombin was not altered by hemoglobin. This study demonstrates that the endothelium of coronary microvessels, like that of larger vessels, importantly modulates vascular reactivity to selected agents. Furthermore, major differences exist between large and small coronary arteries in their response to vasopressin and thrombin.
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PMID:Characteristics of canine coronary resistance arteries: importance of endothelium. 278 67

Two tripeptide analogues (N-[3-methyl-1-S[[2-S [(methyl-amino)carbonyl]-1-pyrrolidinyl] carbonyl]butyl-D-analine) (SC40476) and N-[3-methyl-S-(1-pyrrolidinylcarbonyl)butyl]-D-alanine, ethyl ester, hydrochloride (SC42619], inhibit aggregation of, and secretion from, human platelets induced by thrombin but cause no significant inhibition of esterolysis or fibrin formation catalysed by this enzyme. Inhibition by SC40476 of the aggregatory response induced by thrombin is incomplete. Neither peptide analogue inhibits aggregation induced by ADP, collagen, vasopressin or 11,9-epoxymethanoprostaglandin H2 (U-46619). Enhancement of the response is observed when nonsaturating concentrations of these agonists are employed. SC42619 causes a parallel shift to the right in the concentration-response curve describing aggregation induced by thrombin. The Schild plot of these data has a slope of 1.05 and the pA2 is 2.9 +/- 0.1. Both SC40476 and SC42619 induced a small but significant decrease in the single platelet content of platelet suspensions. Neither peptide analogue increases platelet cytosolic [Ca2+] measured using quin 2 or Fura 2. Both analogues cause inhibition of the increase in cytosolic [Ca2+] induced by thrombin. Inhibition by SC42619 is competitive with respect to thrombin when the extracellular [Ca2+] is reduced to less than 0.1 microM but is non-competitive in the presence of 1 mM Ca2+. SC42619 also inhibits the increase in cytosolic [Ca2+]induced by ADP in the presence of 1 mM Ca2+ but not the smaller increase caused by this agonist when the medium contains less than 0.1 microM Ca2+. SC42619 inhibits Mn2+ influx induced by thrombin and ADP. SC40476 and SC42619 inhibit the enhanced incorporation of [32P] into phosphatidic acid observed on stimulation by thrombin of platelets pre-labelled with [32P]-phosphate. Addition of the peptide analogues alone fails to increase significantly the 32P content of phosphatidate, phosphatidylcholine, phosphatidylserine or phosphatidylethanolamine. SC40476 causes no detectable hydrolysis of glycoprotein V as detected by release of the proteolytic product (glycoprotein VFR). The results indicate that SC40476 and SC42619 interact selectively with the platelet thrombin receptor. Both peptide analogues act as effective antagonists for this receptor but also possess weak agonist activity which may also result from interaction with the thrombin receptor. The molecular basis for this latter activity has not been defined. SC42619 non-selectively inhibits Ca2+ influx induced by several agonists but this effect does not appear to contribute to the observed inhibition of the aggregatory and secretory responses.
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PMID:Identification of small peptide analogues having agonist and antagonist activity at the platelet thrombin receptor. 283 93

Pretreatment of A-10 cells with pertussis toxin had no effect on [arginine]vasopressin-mediated inhibition of cyclic nucleotide accumulation. Pretreatment of the cells with the same concentration of pertussis toxin produced 90-95% inhibition of [32P]ADP ribosylation in membranes, suggesting that these cells possess pertussis-toxin substrate and that the toxin enters the cells to reach its site of action. The functional integrity of the pertussis-toxin substrate in these cells is confirmed by the observation that in these cell membranes increasing concentrations of GTP inhibited basal, forskolin- and NaF-stimulated adenylate cyclase activities, and this inhibition was abolished when the cells were pretreated with pertussis toxin. In addition, thrombin-mediated inhibition of isoprenaline-stimulated cyclic AMP accumulation was also inhibited by pertussis-toxin pretreatment of the cells. These data suggest that, unlike thrombin, [arginine]vasopressin-induced inhibitory effects on cyclic nucleotide accumulation in smooth-muscle cells are not mediated by pertussis-toxin substrate.
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PMID:Inhibition of formation of cyclic AMP and cyclic GMP by vasopressin in smooth-muscle cells is insensitive to pertussis toxin. 284 52

Calf serum induced the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney (NRK) cells transformed by a temperature-sensitive Kirsten murine sarcoma virus (tsK-NRK cells). Various growth factors known to induce the phospholipase C reactions in other cell types, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, thrombin, vasopressin, bombesin, cholecystokinin, and prostaglandin F2 alpha, did not induce phospholipase C reactions in the transformed NRK cells. Furthermore, noradrenaline, histamine, dopamine, angiotensin II, carbachol, and tumor growth factor-beta did not induce phospholipase C reactions. However, serotonin did induce phospholipase C reactions. The amount of serotonin contained in the calf serum was sufficient to support 50% of the activity promoted by the serum itself, and calf serum-induced phospholipase C reactions were inhibited to 10-20% of the original level by ketanserin and methysergide, known to be antagonists for the serotonin receptors. Dialysis almost completely removed serotonin from calf serum and reduced the serum-induced phospholipase C reactions. Moreover, the phospholipase C reactions induced by calf serum and serotonin were inhibited by pretreatment of the cells with pertussis toxin or 12-O-tetradecanoylphorbol-13-acetate. These results indicate that serotonin is one of the major serum factors inducing phospholipase C-mediated hydrolysis of phosphoinositides in transformed NRK cells. Serotonin induced phospholipase C reactions not only in tsK-NRK cells but also in nontransformed NRK cells. However, serotonin did not induce these reactions in Swiss 3T3 cells or NIH 3T3 cells.
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PMID:Serotonin as a major serum factor inducing the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney cells. 284 56


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