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)

1. A new isolated perfused preparation is described that allows a direct comparison to be made of the responses of the perfused arterial and retrogradely perfused venous circulations of the rat superior mesenteric vascular bed. 2. In experiments comparing the responses of the intact arterially perfused mesentery and small intestine to those of the same preparation following removal of the intestine and division of the circulations, the increases in perfusion pressure produced by arginine-vasopressin (30 pmol) and noradrenaline (1 nmol) were retained by the arterial circulation and those induced by angiotensin II (30 pmol) by the venous circulation. Endothelin-1 (30 pmol) constricted both portions of the vasculature but the prolonged nature of its response was associated with only the venous vessels. 3. In the simultaneously perfused arterial and venous preparation arginine vasopressin (3-100 pmol) was a selective constrictor of the arterial circulation and angiotensin II (3-100 pmol) of the venous circulation. In addition, noradrenaline (0.3-10 nmol), 5-hydroxytryptamine (0.3-10 nmol) and KCl (1-60 micromol) were more active as constrictors of the arterial than the venous vessels, and U46619 (10-300 pmol) a more active constrictor of the venous than the arterial vessels. Endothelin-1 (3-100 pmol) constricted both the arterial and venous portions of the vasculature but was significantly longer acting as a venoconstrictor than an arterioconstrictor. 4. Angiotensin I (300 pmol) caused constrictions of the venous circulation which were dependent upon the presence of angiotensin converting enzyme for captopril (10 microM) abolished constrictions caused by angiotensin I but not by angiotensin II. 5. In preparations preconstricted by U46619 (0.3-3 microM), acetylcholine (0.01-100 nmol), bradykinin (0.001-nmol), sodium nitroprusside (0.01-lOnmol) or isoprenaline (1-l00pmol) produced dose-related dilatations of both the arterial and the venous vasculatures, whereas adenosine diphosphate (ADP, 0.01-lOOnmol) caused dose-dependent dilatations of the arterial circulation but principally constrictions of the venous circulation. The dilatations caused by acetylcholine and bradykinin in both portions of the circulation, and by ADP in the arterial circulation, were endothelium-dependent as they were inhibited by gossypol (3 microM), whereas dilatations to sodium nitroprusside were not. 6. This preparation allows the responses of the arteries and veins of a single perfused mesenteric bed to be compared. In addition, with this preparation it is possible to demonstrate that veins, as well as arteries, show significant endothelium-dependent relaxations. It is concluded that the venous portion of the vasculature is significantly involved in the responses of the intact circulation.
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PMID:Simultaneous perfusion of rat isolated superior mesenteric arterial and venous beds: comparison of their vasoconstrictor and vasodilator responses to agonists. 232 5

The regulation of receptor-operated calcium channels of human platelets by phospholipid-dependent, Ca2+- and diacylglycerol-activated protein kinase C was studied. In order to induce the activation of endogenous protein kinase C, a cell-penetrable structural diacylglycerol analog, 4 beta-phorbol 12 beta-myristate-13 alpha-acetate (FMA), was used. Using two independent approaches, i. e., the fluorescent probe for Ca2+, quin-2, and 45Ca2+ absorption technique, it was demonstrated that FMA (10(-10) - 10(-8) g/ml) blocks Ca2+ influx into the platelets induced by aggregation factors, e. g., ADP, vasopressin, platelet activating factor, thrombin and thromboxane A2 receptor agonist U46619. The half-maximum inhibition of the receptor-sensitive influx of Ca2+ was observed at (3-6) X 10(-10) g/ml of FMA. Under physiological conditions, protein kinase C is activated with an increase in Ca2+ concentration in the cytoplasm in the presence of diacylglycerol. Since the above-mentioned inducers besides Ca2+ influx stimulate diacylglycerol synthesis, it was assumed that the activation of protein kinase C triggers a negative feedback mechanism which blocks the receptor-operated calcium channels.
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PMID:[Blocking with phorbol ester, a protein kinase C activator, of receptor-dependent platelet calcium channels]. 241 59

The effect of calcium antagonists (verapamil, nicardipine, nifedipine), nitrates (glycerin trinitrate, isosorbide dinitrate and sodium nitroprusside) and of antiarrhythmic drugs (ethmozin, ethacizin) on the increase of platelet Ca2+ concentration brought about by aggregation inductors was studied. All the analyzed substances produced an inhibitory effect on the induction of cellular Ca2+ level increase due to the action of platelet aggregation factor, ADP, vasopressin and endoperoxide PGH2 stable analogue. The degree of this inhibitory effect of calcium antagonists and nitrates was independent of the nature of the stimulator used. Calcium-blocking action of calcium antagonists and nitrates was due to suppression of the entry of Ca2+ into the cells. The action of nitrates on platelets was accompanied by an acceleration of cGMP and cAMP synthesis. Unlike nitrates, antiarrhythmic drugs did not influence the intracellular level of cyclic nucleotides. On the basis of the data obtained it is suggested that calcium-blocking action of different types of compounds can be mediated by different intracellular mechanisms.
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PMID:[Blockade of thrombocyte calcium channels by cardiotropic compounds]. 243 7

The adenylate-cyclase activator forskolin, the guanylate-cyclase stimulator sodium nitroprusside, the phosphodiesterase inhibitor Ro 15-2041, different Ca-entry blockers, as well as various vasodilators, and the atrial natriuretic peptide were tested for antiplatelet activity. Thrombin, vasopressin, ADP, arachidonic acid, and the dihydropyridine Ca agonist CGP 28392 were used as platelet activators. The physiological and biochemical parameters of platelet function studied included shape-change reaction, intracellular free-Ca modulation, and cyclic nucleotide formation. When inhibition of the shape-change response occurred, it was accompanied by inhibition of the increase in intracellular free Ca. Furthermore, the results suggest a possible intracellular site of action of Ca entry blockers in platelets, and confirm the importance of modulation of cyclic nucleotides in the regulation of platelet function, regardless of the mechanism of platelet activation. Additional antiplatelet activity of antihypertensive agents may have a beneficial effect in reducing the associated risk of thrombo-embolic complications in essential hypertension.
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PMID:Vasodilating agents and platelet function: intracellular free calcium concentration, cyclic nucleotides, and shape-change response. 243 9

At least two signal-generating systems are involved in the actions of various hormonal factors in human platelets--the adenylate cyclase system and the phosphoinositide-metabolizing pathway. The formation of cyclic AMP (cAMP) by the adenylate cyclase system--consisting of the catalyst itself, the Ns and Ni proteins, and various hormone receptors--is stimulated by prostaglandins and adenosine, and is inhibited by alpha 2-adrenergic agonists, ADP, vasopressin, platelet-activating factor, and thrombin. On the other hand, the formation of inositol trisphosphate and diacylglycerol by the phosphoinositide-metabolizing pathway is stimulated by some of the latter agents, particularly by thrombin. There are apparently several mutual interactions between these two signal-generating systems. On the one hand, increases in the level of cAMP inhibit the formation of inositol phosphates and diacylglycerol. It is presently unclear whether this inhibitory effect of cAMP is due to a direct action at the phospholipase C itself or to an indirect mechanism, for example, a depletion of the substrate of the enzyme. On the other hand, protein kinase C, which is activated by diacylglycerol, largely interferes with the adenylate cyclase system. This kinase, when activated by diacylglycerol or phorbol esters, apparently phosphorylates the guanine nucleotide-binding alpha-subunit of Ni, which results in an impairment or loss of the inhibitory hormonal signal transduction to the adenylate cyclase. Thus, available evidence indicates that the two signal-generating systems present in platelet membranes are not completely separated, and furthermore suggests that they may even be causally related to each other.
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PMID:Interactions between the hormone-sensitive adenylate cyclase system and the phosphoinositide-metabolizing pathway in human platelets. 243 28

Jakobs, Bauer & Watanabe [(1985) Eur. J. Biochem. 151, 425-430] reported that treatment of platelets with phorbol 12-myristate 13-acetate (PMA) prevented GTP- and agonist-induced inhibition of adenylate cyclase in membranes from the platelets. This was attributed to the phosphorylation of the inhibitory guanine nucleotide-binding protein (Gi) by protein kinase C. In the present study, the effects of PMA on cyclic [3H]AMP formation and protein phosphorylation were studied in intact human platelets labelled with [3H]adenine and [32P]Pi. Incubation mixtures contained indomethacin to block prostaglandin synthesis, phosphocreatine and creatine kinase to remove ADP released from the platelets, and 3-isobutyl-1-methylxanthine to inhibit cyclic AMP phosphodiesterases. Under these conditions, PMA partially inhibited the initial formation of cyclic [3H]AMP induced by prostaglandin E1 (PGE1), but later enhanced cyclic [3H]AMP accumulation by blocking the slow decrease in activation of adenylate cyclase that follows addition of PGE1. PMA had more marked and exclusively inhibitory effects on cyclic [3H]AMP formation induced by prostaglandin D2 and also inhibited the action of forskolin. Adrenaline, high thrombin concentrations and, in the absence of phosphocreatine and creatine kinase, ADP inhibited cyclic [3H]AMP formation induced by PGE1. The actions of adrenaline and thrombin were attenuated by PMA, but that of ADP was little affected, suggesting differences in the mechanisms by which these agonists inhibit adenylate cyclase. sn-1,2-Dioctanoylglycerol (diC8) had effects similar to those of PMA. The actions of increasing concentrations of PMA or diC8 on the modulation of cyclic [3H]AMP formation by PGE1 or adrenaline correlated with intracellular protein kinase C activity, as determined by 32P incorporation into the 47 kDa substrate of the enzyme. Parallel increases in phosphorylation of 20 kDa and 39-41 kDa proteins were also observed. Platelet-activating factor, [Arg8]vasopressin and low thrombin concentrations, all of which inhibit adenylate cyclase in isolated platelet membranes, did not affect cyclic [3H]AMP formation in intact platelets. However, the activation of protein kinase C by these agonists was insufficient to account for their failure to inhibit cyclic [3H]AMP formation. Moreover, high thrombin concentrations simultaneously activated protein kinase C and inhibited cyclic [3H]AMP formation. The results show that, in the intact platelet, the predominant effects of activation of protein kinase C on adenylate cyclase activity are inhibitory, suggesting actions additional to inactivation of Gi.
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PMID:Effects of activation of protein kinase C on the agonist-induced stimulation and inhibition of cyclic AMP formation in intact human platelets. 244 6

The effect of antihypertensive drugs on receptor-dependent increase in Ca2+ basal level and its changes under stimulators action (thrombocytes activating factor, ADP and vasopressin) were studied by means of a fluorescent calcium probe "quin-2". Nifedipine blocked receptor-dependent increase of Ca2+ in thrombocytes in vitro as well as by oral administration, which was accompanied by decrease in vascular tone and BP. The degree of BP decrease correlated with that of depression of receptor-dependent increase of Ca2+ in thrombocytes. Combined therapy including nifedipine, propranolol and a diuretic resulted in more manifest inhibition of receptor-dependent calcium channels than monotherapy with nifedipine. Effect of antihypertensive drugs evidently depends on their influence on receptor-dependent Ca2+ cellular entrance.
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PMID:[Effect of hypotensive therapy on a receptor-dependent increase in Ca2+ in the thrombocytes of patients with hypertension]. 245 72

Some studies have indicated that insulin was able to increase the level of free cytosolic calcium in adipocytes [e.g. 7]. The present study was designed to examine this phenomenon. Insulin did not increase free cytosolic calcium, however oxytocin, vasopressin, alpha-adrenergic agonists and ATP did increase free cytosolic calcium in adipocytes. Other agonists which also did not alter calcium were epidermal growth factor, angiotensin II, glucagon, and beta-adrenergic agonists. The effect of oxytocin at increasing free cytosolic calcium was inhibited by activation of protein kinase C with phorbol 12-myristate 13-acetate and by ADP ribosylation of a Gi like protein with islet activating protein. The hormones that did increase cytosolic free calcium did so by mobilizing internal calcium and by promoting calcium influx. Even though insulin did not increase free cytosolic calcium, it was able to attenuate the alpha-adrenergic mediated increase in cytosolic free calcium. The fact that certain hormones can increase the level of the second messenger calcium in adipocytes implies that it may be a key intracellular regulator of adipocyte function as it is in many other tissues.
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PMID:Effect of hormones on cytosolic free calcium in adipocytes. 251 19

Vasopressin (V2) receptors were solubilized from porcine kidney membranes with the detergent egg lysolecithin. Binding of [3H]vasopressin to the solubilized fraction was rapid, specific, and saturable. The agonist dissociation constants observed in membranes and solubilized fractions were 1.7 +/- 0.3 and 2.3 +/- 0.2 nM, respectively. In competition binding experiments, the solubilized fraction exhibited the same pharmacological profile as the membranes. Chemical crosslinking of [125I]vasopressin to the solubilized fraction followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated a 62-kDa band which was specifically labeled with [125I]vasopressin. Vasopressin binding sites from the solubilized fractions were resolved by gel filtration and ultracentrifugation on a sucrose gradient. In addition, agonist high affinity binding to V2 receptors and its sensitivity to guanine nucleotides were preserved even after solubilization in the absence of prebound agonist prior to solubilization. Addition of guanine nucleotides such as GTP gamma S decreased the specific binding of [3H]arginine vasopressin to these solubilized fractions in a dose-dependent manner, suggesting the solubilization of a V2 receptor-G protein complex. [32P]ADP ribosylation of the solubilized fraction by cholera and pertussis toxins revealed specifically labeled proteins with molecular weights of 42,000-43,000 and 39,000-41,000, respectively, on sodium dodecyl sulfate polyacrylamide gels. Furthermore [35S]GTP gamma S binding to these solubilized fractions was enhanced by vasopressin, confirming that a significant proportion of the vasopressin receptors must be closely coupled to G proteins even when these receptors are solubilized in the absence of agonist. These results are in contrast with those reported for beta, alpha 2 adrenergic and D2 dopaminergic receptor systems, but in agreement with D1 dopaminergic and A1 adenosine receptors. The molecular mechanism responsible for this difference remains to be determined.
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PMID:Solubilization of a guanine nucleotide-sensitive form of vasopressin V2 receptors from porcine kidney. 252 56

As previously described, WRK1 plasma membrane possesses a vasopressin-sensitive phospholipase C [G. Guillon et al., 1986, FEBS Lett. 196, 155-159]. In the present study, we examined the sensitivity of this enzyme to guanylnucleotides. GTP gamma S induces a time- and dose-dependent stimulation of Ins(1,4,5)P3 and Ins(1,4)P2 accumulation. No accumulation of InsP1, Ins(1,3,4)P3 or Ins(1,3,4,5)P4 occurred under similar conditions. Gpp(NH)p produced the same effect but was less potent. GTP and a nonhydrolyzable analogue of ATP, App(NH)p, were without effect. Calcium also stimulated the phospholipase C activity in a time- and dose-dependent manner. In the absence of calcium, the activity of GTP gamma S was considerably reduced. Physiological calcium concentrations (between 10(-8) and 10(-7) M), allowed maximal GTP gamma S stimulation of phospholipase C activity. In this system, the presence of vasopressin alone did not generate inositol phosphate accumulation. However, this hormone: (i) reduced the lag-time observed during GTP gamma S stimulation, (ii) increased the sensitivity of phospholipase C to GTP and to GTP gamma S, and (iii) did not modify the stimulation of phospholipase C induced by maximal doses of GTP gamma S. Unlike sodium fluoride, GTP gamma S elicited an irreversible activation of phospholipase C. Calcium, GTP gamma S and sodium fluoride stimulated the phospholipase C activity via mechanisms sharing a common step, since their maximal effects were not additive. Cholera toxin treatment, known to produce complete ADP-ribosylation of 'alpha s' subunits, partially reduced the basal and the maximal GTP gamma S-mediated stimulation of phospholipase C activity as well as that caused by vasopressin. This inhibition was not mimicked by treatment with either forskolin or pertussis toxin.
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PMID:Properties of membranous phospholipase C from WRK1 cell: sensitivity to guanylnucleotides and bacterial toxins. 253 43


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