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)

Isolated rat hindlimbs were perfused at 37 degrees C and constant physiological pressure (80 +/- 0.5 mmHg) while the flow rate that was allowed to freely self-adjust was monitored. Under these conditions, evidence was obtained for both alpha- and beta-adrenergic stimulation of oxygen consumption (VO2) in contrast to constant-flow perfusion, which has only convincingly shown alpha-adrenergic stimulation of VO2 in response to adrenergic agents. Addition of norepinephrine (NE; 1-33 nM) led to an increase in VO2 with a maximum of 29% above the basal value at 3.3 nM, even though the flow rate decreased. Phenylephrine (3.3-33 nM) and vasopressin (10-100 pM) also showed similar, but lesser in magnitude, vasoconstriction-associated stimulatory effects on VO2. Prazosin (an alpha 1-antagonist) completely reversed the NE-mediated decrease in flow rate and significantly blocked the increased VO2. In contrast, isoproterenol (10-1,000 nM) increased both flow rate (30%) and VO2 (32%). The isoproterenol-stimulated VO2 was not blocked by the beta 1-, beta 2-antagonist propranolol (10 microM), although the increased flow was reversed. In the presence of propranolol (1 or 10 microM), BRL-35135A (a beta 3-agonist) also stimulated VO2 (18%) without significant change in flow rate. These results lend further support to the role of the alpha 1-adrenoceptor in muscle VO2. In addition there is evidence for the presence of a functional beta 3-adrenoceptor as an additional subtype responsible for NE-mediated thermogenesis in the rat hindlimb.
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PMID:Constant-pressure perfusion of rat hindlimb shows alpha- and beta-adrenergic stimulation of oxygen consumption. 749 49

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.
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PMID:Antianginal effects of YM-16151-4 in various experimental angina models. 768 38

We investigated effects of beta-adrenoceptor agonists (beta 1-selective: T-1583 and dobutamine, beta 2-selective: fenoterol, non-selective: isoproterenol) on urine outflow rate, blood pressure, heart rate, respiratory rate and rectal temperature. The drugs were applied into the paraventricular nuclei (PVN) of spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Wistar rats. Fenoterol and isoproterenol markedly decreased the urine outflow rate, compared with T-1583 and dobutamine in the rats. There was no marked difference among the three strains in responsiveness to fenoterol and isoproterenol. The antidiuretic effects of fenoterol were inhibited by a beta 2-selective antagonist, butoxamine, more markedly than a beta 1-selective antagonist, atenolol, in SHR; and the inhibitory effects of these drugs were partial in WKY. In Wistar rats, the effect of fenoterol was inhibited by a non-selective beta-antagonist, timolol, but not by atenolol or butoxamine. A vasopressin antagonist (i.v.) did not diminish the antidiuretic effect of fenoterol. Fenoterol reduced the blood pressure in SHR and WKY, but not in Wistar rats. It was suggested that there were predominantly beta 2-adrenoceptors mediating antidiuresis in SHR. In WKY and Wistar rats, however, the beta-adrenoceptor subtypes mediating antidiuresis have yet to be determined. The ability of beta-adrenoceptor agonists to decrease urine outflow rates in SHR was not altered as compared to that in the control rats. beta-Adrenoceptor-mediated antidiuresis was not due to vasopressin release.
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PMID:Effects of beta 1- and beta 2-adrenoceptor agonists applied into the hypothalamic paraventricular nuclei of spontaneously hypertensive rats on urine production. 791 52

We studied the relative ability to activate phospholipase C (PLC) of four Gs-coupled receptors expressed in L cells at different densities. Stable cell lines expressing various levels of the luteinizing hormone receptor (LHR), the type 2 vasopressin receptor (V2R), or the type 1 or type 2 beta-adrenergic receptor (beta 1- or beta 2AR) were isolated. The PLC activity was assessed by the measurement of free intracellular Ca2+ concentrations and the accumulation of inositol phosphates. We previously reported that, at 24,000 sites/cell, the LHR in L cells stimulated adenylyl cyclase by 10-fold over basal levels and PLC by 50% over basal levels. The EC50 for stimulation was 20-fold higher for PLC than for adenylyl cyclase. We now report that LHR tends to stimulate PLC more at a higher receptor density and less at a lower density. EC50 values for accumulation of inositol phosphates remained unchanged. The human V2R and the human beta ARs are strong adenylyl cyclase stimulators, and their potential for dual signaling was unknown. Expressing the V2R at 100,000 sites/cell or more and the beta ARs at 300,000 sites/cell resulted in stimulation of PLC by these receptors. As with the LHR, higher concentrations of vasopressin or isoproterenol were needed to reach 50% stimulation of PLC, compared with that of adenylyl cyclase. The beta 1AR was a stronger PLC stimulator than was the beta 2AR. The orders of potency for isoproterenol, epinephrine, and norepinephrine to stimulate adenylyl cyclase and PLC were the same for each of the two beta ARs. These results indicate that the ability of Gs-coupled receptors to stimulate PLC is dependent on the levels of receptor expression, and they suggest that dual signaling potential is a common property of Gs-coupled receptors and possibly also of G(i)-coupled receptors.
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PMID:Dual signaling potential is common among Gs-coupled receptors and dependent on receptor density. 793 26

The testis is a complex organ in which local control is achieved by signalling between its constituent cells. Herein we describe the responses of cultured rat testicular cells and a mouse Sertoli cell-line to stimulation by endothelin and ATP, and elsewhere we have shown that rat peritubular myoid cells possess phosphoinositidase C-coupled V1a-vasopressin receptors identical to those of liver (Howl, J. et al, 1995, Endocrinology 136: 2206-2213). 1. Peritubular myoid cells from pre-pubertal rats responded through ETA receptors with PtdIns(4,5)P2 hydrolysis [EC50 for endothelin-1 (ET-1) approximately 0.4 nM], elevation of intracellular [Ca2+], and tyrosine phosphorylation of a variety of cellular proteins. They also showed enhanced adenylate cyclase activity, with an EC50 for ET-1 of approximately 3 nM, also through ETA receptors. Pharmacological elevation of [cAMP] did not immediately change the ET-1-stimulated formation of inositol phosphates, but attenuated the response after several hours. 2. Pre-pubertal rat Sertoli cells showed no detectable responses to ET-1, but responded to FSH with elevated [cAMP] and to ATP with PtdIns(4,5)P2 hydrolysis. PtdIns(4,5)P2 hydrolysis was equally responsive to ATP and UTP, and so appears to be activated by P2U-purinergic receptors. This response was enhanced by protein kinase C inhibition and attenuated by PKC activation. 3. Despite its lack of effect on rat Sertoli cells in primary culture, ET-1 provoked PtdIns(4,5)P2 hydrolysis in the TM4 murine Sertoli cell line (EC50 approximately 0.6 nM), and this response was negatively regulated by protein kinase C activation. 5. No receptor-stimulated activation of phosphoinositase C was detected in 'germ cell' populations, but the non-specific G protein activator A1F4-provoked inositol phosphate accumulation in these cells, so demonstrating their potential to respond through yet to be identified G protein-coupled receptors with phosphoinositidase C activation. 6. Immunoblotting studies showed the presence in rat testis of phosphoinositidase C-beta 1 and the alpha-subunits(s) of the G-protein(s) Gq and/or G11. These studies show that testicular myoid and Sertoli cells use at least three G protein-coupled receptors (V1a-vasopressins, ETA-endothelin and P2U-purinergic) to signal through phosphoinositidase C activation, that ET-1 can activate multiple signalling pathways in myoid cells, and that the ET-1-stimulated phosphoinositidase C responses of myoid and Sertoli cells have different regulatory characteristics.
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PMID:Inositol lipid-mediated signalling in response to endothelin and ATP in the mammalian testis. 856 25

Changes in the release of atrial natriuretic peptide (ANP) and vasopressin (VP) may contribute to the final outcome of beta-adrenoceptor blocking therapy. Therefore, we administered 2 hours before a bicycle exercise test (a 30-minute exercise with 100 W work load) in a randomized, double-blind, placebo-controlled crossover study orally 50 mg atenolol, 80 mg propranolol or 10 mg pindolol to 15 healthy volunteers. Hormone release and sympathoadrenal activation were estimated by measuring plasma ANP-, VP-, adrenaline and noradrenaline concentrations. beta-blockade and -antagonism were estimated by measuring the reduction of exercise-induced tachycardia and the extent to which the drugs occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors in the circulating plasma. We noticed clear differences in the animal beta 1- and beta 2-receptor occupancy between these agents. The agents and placebo during the exercise augmented plasma ANP level similarly, on average by 34-72%. Pindolol administration enhanced the decline of plasma ANP level after exercise (ANCOVA rep meas, pindolol vs placebo, p < 0.05). Although pindolol increased the mean plasma VP level by 25% (ANCOVA rep meas for the increase, pindolol vs placebo, p < 0.05), drug effects on plasma VP-level were generally negligible. In conclusion, in healthy volunteers beta 1- and beta 2-antagonism by pindolol, atenolol and propranolol do not markedly potentiate plasma ANP- and VP-responses to physical exercise. The responses are, however, slightly influenced presumably by the beta-agonist activity of pindolol.
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PMID:beta-blockade, atrial natriuretic peptide and exercise. 868 91

Since iron has been implicated as a potential nephrotoxin, we examined the effect of iron on several aspects of cultured renal tubular epithelial cell biology. We found that exposure to 10(-4) M of either the ferrous or ferric form of iron impaired healing of denuded areas made within confluent monolayers of LLC-PK1 cells. This impairment required 30 to 80 hours of exposure to iron to occur and was also seen in another renal tubular epithelial cell line (MDCK cells). To delineate the potential mechanism(s) of this impairment, we examined the expression of a key integrin subunit involved in cell-matrix adhesion. Exposure of LLC-PK1 cells to 10(-4) M ferric citrate for 72 hours significantly decreased expression of the beta 1 integrin subunit as determined by flow cytometry. To determine if iron impairs another process that occurs at the basolateral surface, the effects of 72 hours of exposure to iron on adenylate cyclase activity were examined. Both ferric and ferrous citrate significantly enhanced vasopressin- and forskolin-stimulated adenylate cyclase activity. To examine if iron can regulate proliferation, the effect of iron on 3H-thymidine uptake was measured. We found that ferric citrate diminished proliferation and this decrease required the presence of either serum or transferrin. To ascertain if iron affected ultrastructure, we used transmission electron microscopy and found that iron accumulation within cells was much more apparent with ferric than ferrous citrate. Ferric iron induced mild-to-moderate cytopathic changes. These results indicate that iron is capable of inducing multiple changes in renal tubular epithelial function. The effect of iron to impair wound healing may be related to diminished expression of the beta 1 integrin subunit and perhaps to impaired proliferation.
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PMID:Effect of iron on renal tubular epithelial cells. 884 Feb 71

Rat liver plasma membranes reconstituted with bovine brain phospholipase C beta 1 (PLC- beta 1) exhibit a dual regulation of PLC- beta 1 activity by G-proteins. Guanosine 5'-[gamma-thio]triphosphate (GTP[S]; 0.1 nM) produced a 20-25% inhibition of PLC- beta 1 activity within 7 min of incubation. The addition of vasopressin resulted in near-basal levels of activity in the presence of 0.1 nM GTP[S]. Clonidine had little effect on the net inhibition due to GTP[S]. A similar antagonism between carbachol and GTP[S] occurred in cerebral cortical membranes containing endogenous PLC- beta 1 activity. alpha 0/i-GDP (a mixture of GDP-liganded G0 alpha and Gi alpha) attenuated the GTP[S]-dependent inhibition of PLC- beta 1 whereas alpha 0/i-GTP[S] had no effect, suggesting an involvement of G-protein beta gamma subunits in the inhibition of PLC- beta 1. Low concentrations of beta gamma subunits inhibited PLC- beta 1 activity. Inhibition was followed by reversal to basal activity and onset of stimulation as the beta gamma concentration was increased. Inhibition by beta gamma was dependent on the presence of membranes. These results indicate that G-protein beta gamma subunits constitute a mechanism by which G-protein mediate a rapid and transient inhibition of PLC- beta 1.
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PMID:G-protein inhibition of phospholipase C-beta 1 in membranes: role of G-protein beta gamma subunits. 887 Jun 65

gamma 2-Melanocyte-stimulating hormone (gamma 2-MSH) and related melanotropins have been shown to have various cardiovascular effects, including acute, short-lasting increases in blood pressure (MAP) and heart rate (HR). gamma 2-MSH, administered intravenously, dose-dependently increased MAP and HR with an ED50 of approximately 30 nmol/kg and a maximal effect on MAP of approximately 55 mm Hg and on HR of around 70 beats per minute. Intravenous (i.v.) pretreatment with the alpha 1-adrenoceptor antagonist, prazosin, caused the dose-response curve for the effect of gamma 2-MSH on MAP to shift to the right with a decrease in slope, whereas it had no effect on the dose-response curve for the effect on HR. I.v. pretreatment with the beta 1-adrenoceptor antagonist, metoprolol, had no effect on the dose-response curve for the effect of gamma 2-MSH on MAP, but it caused the dose-response curve for the effect of the peptide on HR to shift to the right with a decrease in slope. Neither i.v. nor intracerebroventricular (i.c.v.) administration of the vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxy-benzene-sulfonyl)- 3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide), had significant effects on the dose-response curves for the effects of the peptide on either MAP or HR. The doses of prazosin, metoprolol and SR 49059 were found to be effective in counteracting the effects of agonists for these receptors (phenylephrine, isoprenaline and [Arg8]vasopressin, respectively). Taken together, these results support the postulate that the effects of gamma 2-MSH are, at least partially, due to an increase in sympathetic outflow to the periphery (Gruber and Callahan (1989), Am J Physiol 257: R681-R694), and that this increase leads to increased activation of vascular alpha 1-adrenoceptors and cardiac beta 1-adrenoceptors. If, as was suggested by these authors, gamma 2-MSH acts via activation of a central vasopressin system, it is via a vasopressin receptor subtype other than the vasopressin V1A receptor, since i.c.v. administration of a selective vasopressin V1A receptor antagonist failed to interfere with the pressor and cardioaccelerator effects of gamma 2-MSH.
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PMID:Influence of blockade of alpha 1-adrenoceptors, beta 1-adrenoceptors and vasopressin V1A receptors on the cardiovascular effects of gamma 2-melanocyte-stimulating hormone (gamma 2-MSH). 920 56

The mechanism by which glucose and other fuels stimulate phosphoinositide-specific phospholipase C (PLC) in pancreatic islet beta cells is not known. Previous studies have suggested that glucose may couple to PLC beta 1 and PLC delta 1. To determine directly if fuels activate these PLC isozymes, clones stably overexpressing PLC beta 1 or PLC delta 1 were generated in the fuel-sensitive beta cell line RINm5F, and secretagogue regulation of these PLC isoforms was determined. Overexpression of PLC beta 1 or PLC delta 1 significantly increased PLC activity in isolated cell fractions, consistent with overexpression of active PLC isoforms in these clones. In paired experiments, stimulation of inositol phosphate (IP) accumulation by the fuel glyceraldehyde was enhanced in clones overexpressing PLC beta 1, in parallel with the G-protein alpha subunit activator, AlF(4)(-), suggesting a coupling between glyceraldehyde and this PLC isoform. In contrast, overexpression of PLC delta 1 had no effect on glyceraldehyde- or AlF(4)(-)-stimulated IP accumulation. Similarly, IP accumulation stimulated by ionomycin was enhanced in PLC beta 1, but not PLC delta 1 clones, indicating that increases in intracellular free calcium [Ca(2+)](i) can regulate PLC beta 1 but not PLC delta 1 overexpressed in this cell line. Interestingly, [Arg(8)] vasopressin-stimulated, but not carbachol-stimulated, IP accumulation was significantly increased in clones overexpressing either PLC beta 1 or PLC delta 1. These studies illustrate unique pathways coupling diverse secretagogues to specific PLC isoforms in islet beta cells, and demonstrate that glyceraldehyde can activate PLC beta 1 but not PLC delta 1; whereas, vasopressin, but not carbachol, can stimulate either isoform.
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PMID:Fuel and hormone regulation of phospholipase C beta 1 and delta 1 overexpressed in RINm5F pancreatic beta cells. 1137 26


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