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)

The injection of chlorpropamide into Brattleboro homozygous rats (di/di) has previously been shown to result in enhanced activation of renal medullary adenylate cyclase activity and increased renal medullary content of cAMP in response to 1-desamino-8-D-arginine vasopressin (dDAVP). In contrast, in vivo chlorpropamide did not alter GTP, guanylylimidodiphosphate, or fluoride-stimulated adenylate cyclase activities in these renal membranes. We have now found that the effect of in vivo chlorpropamide in enhancing dDVAP-stimulated adenylate cyclase activity involves lowering the Km for ATP. We have also found that dDAVP increases urinary prostaglandin E2 (PGE2) excretion, and treatment with chlorpropamide causes an even greater PGE2 response to dDAVP. In contrast, in vivo chlorpropamide treatment did not increase vascular responses to arginine vasopressin (AVP) in the perfused kidney preparation and, in fact, inhibited the AVP-induced decrease in the glomerular filtration rate. Chlorpropamide, therefore, enhances the renal responses to dDAVP in terms of the cAMP and PG systems, while not increasing responses to postreceptor stimuli of the adenylate cyclase system or vascular responses to AVP. These observations support the concept that in vivo chlorpropamide acts at the receptor of the vasopressin-sensitive part of the tubule to augment responsiveness to vasopressin. In addition, in vivo chlorpropamide may inhibit certain vascular responses to AVP.
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PMID:Further studies on the mechanism by which chlorpropamide alters the action of vasopressin. 695 70

Adenylate cyclase of rat renal cortex was inhibited by angiotensin II (AII). Inhibition required Na+ (100-200 mM) and GTP (10(-8)-10(-4) M) and was opposed by the receptor antagonist [1-sarcosine, 8-isoleucine]AII. The EC50 value (+/- SE)for inhibition by AII was 3.7 +/- 1.2 nM, and the maximum inhibition (+/- SE) was 23 +/- 3%. Inhibition was specific for AII, since both AI and AIII, at concentrations up to 1 microM, were ineffective in producing inhibition. The maximum decrease (+/- SE) in adenylate cyclase activity was from 2.45 +/- 0.08 to 1.78 +/- 0.1 pmol.min/mg protein. A similar absolute decrease was observed when adenylate cyclase was stimulated by calcitonin, vasopressin, or isoproterenol. The inhibition of PTH-stimulated activity [16.7 +/- 0.5 (+/- SE) to 12.2 +/- 0.7 pmol.min/mg protein) was significantly greater than the inhibition of basal activity. Therefore, at least some of the inhibitory angiotensin receptors are coupled to adenylate cyclase molecules which also coupled to receptors for PTH.
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PMID:Inhibition of adenylate cyclase by angiotensin II in rat renal cortex. 712 30

Rat aortic smooth muscle cells produced large quantities of nitric oxide (NO) after exposure to interleukin-1 beta, and this was depressed in the presence of the protein kinase C inhibitor bisindolylmaleimide. Intracellular cAMP levels were elevated mildly in cytokine-treated smooth muscle cells, and the presence of forskolin enhanced both the cAMP levels and NO production. Inhibition of GTP:cyclohydrolase I by 2,4-diamino-6-hydroxypyrimidine attenuated NO production by interleukin-1 beta-treated cells. GTP:cyclohydrolase is the regulatory enzyme for de novo tetrahydrobiopterin synthesis, and the latter is a required cofactor for NO synthase activity. Treatment of smooth muscle cells with forskolin induced GTP:cyclohydrolase mRNA expression, and simultaneous treatment of cells with forskolin and phorbol esters elicited NO production. Angiotensin II and arginine-vasopressin, acknowledged agonists for protein kinase C, elicited production of NO by forskolin-treated smooth muscle cells. These observations confirm the importance of GTP:cyclohydrolase activity for NO production by cultured smooth muscle cells and implicate both adenylyl cyclase and protein kinase C in this process.
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PMID:Simultaneous activation of adenylyl cyclase and protein kinase C induces production of nitric oxide by vascular smooth muscle cells. 752 13

The substance P (SP) analogues [DArg1, DPhe5, DTrp7,9, Leu11] SP (AntD) and [Arg6, DTrp7,9, MePhe8] SP (6-11) (AntG) inhibit the action of many different neuropeptides including SP. These analogues might be useful in the treatment of small cell lung cancer but their mechanism of action is unclear. Here, we analyzed the effect of AntD and AntG on neuropeptide vs. guanosine 5'-3-O-(thio) triphosphate (GTP gamma S)-stimulated inositol phosphate generation in permeabilized Swiss 3T3 cells. AntD inhibited vasopressin and bombesin stimulated inositol phosphate formation (IC50 of 0.75 microM and 2 microM, respectively). Similarly, AntG inhibited vasopressin-stimulated inositol phosphate generation with an IC50 of 1 microM. Strikingly, neither AntD up to 10 microM nor AntG up to 20 microM was able to inhibit GTP gamma S-stimulated inositol phosphate generation. Dose-response curves of neuropeptide-induced inositol phosphate generation were dramatically displaced to the right by either 10 microM AntD or 20 microM AntG. However, neither antagonist affected the dose response of GTP gamma S-stimulated inositol phosphate generation. Furthermore, 20 microM AntD had no effect on AIF-4-induced inositol phosphates in COS-1 cells transfected with G alpha q. AntD inhibited [3H]vasopressin binding competitively in intact Swiss 3T3 cells and both AntD and AntG inhibited [3H]vasopressin binding in Swiss 3T3 and rat liver membranes. Scatchard analysis revealed that AntD inhibited vasopressin binding by reducing receptor affinity without affecting receptor number in both intact and membrane preparations of Swiss 3T3 cells. The results strongly suggest that SP analogues AntD and AntG block the action of the Ca2+ mobilizing neuropeptides at the receptor level, rather than inhibiting G protein-stimulated inositol phosphate production.
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PMID:Substance P-related antagonists inhibit vasopressin and bombesin but not 5'-3-O-(thio)triphosphate-stimulated inositol phosphate production in Swiss 3T3 cells. 753 71

In the toad urinary bladder, antidiuretic hormone (ADH)-mediated changes in water permeability depend on exocytic insertion and endocytic retrieval of water channels into and from the apical membrane, respectively. Because GTP-binding proteins (G proteins) are well-recognized regulators of vesicular trafficking throughout the cell, we tested the hypothesis that drugs interfering with G protein would modify the hydrosmotic response to ADH and the ADH-regulated formation of endosomes, as assessed by luminal incorporation of a fluid-phase marker [fluorescein isothiocyanate (FITC)-dextran, 70 kDa]. Mastoparan (4 microM) and compound 48/80 (poly-p-methoxyphenylethylmethylamine; 50 micrograms/ml), added to the luminal side of the toad urinary bladder, as well as AlF3 added to the serosal side (400 microM), inhibited ADH- and 8-bromoadenosine 3',5'-cyclic monophosphate-induced transepithelial water flow by > 50% and simultaneously enhanced cellular incorporation of FITC-dextran by > 200%. The pattern of FITC-dextran uptake observed using fluorescence microscopy both in scraped cells and in the intact bladder was granular, suggesting fluid-phase endocytosis. Mastoparan and AlF3, which are both probes of G proteins, increased FITC-dextran uptake only in the presence of ADH and a transepithelial osmotic gradient, i.e., under conditions where water channel-carrying endosomes presumably cycle. Therefore, we suggest that the ADH-dependent cycling of water channels could be controlled by one or more G proteins associated with the apical membrane and/or the water channel-carrying vesicles.
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PMID:Drugs activating G proteins disturb cycling of ADH-dependent water channels in toad urinary bladder. 754 30

Bombesin- and vasopressin-stimulated phospholipase D (PLD) activities are rapidly desensitized in 3T3 cells, in addition both agonists are subject to heterologous desensitization. Binding studies showed that homologous desensitization was partly a result of loss of cell surface receptors, whilst heterologous desensitization was independent of receptor changes. Pretreatment with either agonist reduced subsequent GTP gamma S-stimulated PLD activity by 50% whereas a pretreatment with GTP gamma S did not attenuate the response, suggesting that the G-protein or downstream effector systems were affected by receptor activation resulting in desensitization. The desensitization of receptor-stimulated PLD activation provides support for the phospholipase functioning in a key signalling pathway.
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PMID:Heterologous desensitization of bombesin- and vasopressin-stimulated phospholipase D activity in Swiss 3T3 fibroblasts. 769 16

Extracellularly added adenosine and ATP are potent inhibitors of protein synthesis in liver cells. In this study, the possible involvement of Ca2+ in the mechanism of inhibition of protein synthesis by adenosine was investigated. Stimulation of freshly isolated hepatocytes with adenosine or ATP, at concentrations that impaired protein synthesis, induced an increase in the cytosolic free Ca2+ concentration ([Ca2+]i). However, there was no correlation between the increase in [Ca2+]i and inhibition of radiolabelled leucine incorporation into proteins. Thus, the stimulation of hepatocytes with the V1-receptor agonist, vasopressin, or with the nucleotide triphosphates, UTP and GTP, elicited changes in [Ca2+]i similar to those observed after ATP or adenosine addition, but did not affect protein synthesis. ATP produced near complete discharge of Ca2+ from the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in isolated hepatocytes, whereas adenosine only had a partial effect. Depletion of the hormone-sensitive Ca2+ pool by adenosine was transient. In contrast, prolonged depletion of internal Ca2+ by thapsigargin resulted in the inhibition of protein synthesis in hepatocytes. However, the inhibition of radiolabelled leucine incorporation into proteins by thapsigargin was further augmented by the additional presence of adenosine. These results show that the inhibition of protein synthesis by adenosine in isolated hepatocytes is not mediated by an increase in [Ca2+]i or depletion of internal pool(s) sensitive to inositol 1,4,5-trisphosphate or thapsigargin.
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PMID:Adenosine inhibits protein synthesis in isolated rat hepatocytes. Evidence for a lack of involvement of intracellular calcium in the mechanism of inhibition. 774 64

The ability of 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122), an inhibitor of phospholipase C (Smith et al., J Pharmacol Exp Ther 253:688-697, 1992), to inhibit agonist-stimulated and store-operated Ca2+ inflow in single hepatocytes was investigated with the aim of testing whether the activation of phospholipase C is a necessary step in the process of agonist-stimulated Ca2+ inflow in this cell type. U73122 inhibited the release of Ca2+ from intracellular stores and plasma membrane Ca2+ inflow induced by vasopressin. An inactive analogue of U73122, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]- 2,5-pyrrolidone-dione (U73433), did not inhibit vasopressin-induced release of Ca2+ from intracellular stores, but did partially inhibit Ca2+ inflow. Neither U73122 nor 'inactive' analogue U73433 inhibited the release of Ca2+ from intracellular stores when this was initiated by the photolysis of 'caged' guanosine (5'-[gamma-thio]triphosphate (GTP gamma S) introduced to the cytoplasmic space by microinjection. However, both compounds inhibited GTP gamma S-stimulated Ca2+ inflow. U73122 also inhibited the actions of glycerophosphoryl-myo-inositol-4,5-diphosphate (GPIP2), a slowly-hydrolysed analogue of inositol 1,4,5-triphosphate (InsP3) which is released by photolysis of 'caged' 1-(alpha-glycerophosphoryl)-myo-inositol-4,5-diphosphate, P4(5)-1-(2-nitrophenyl)ethyl ester, and thapsigargin in stimulating Ca2+ inflow. U73122 did not inhibit GPIP2-stimulated release of Ca2+ from intracellular stores, but did partially inhibit the ability of thapsigargin to induce Ca2+ release. It is concluded that, while U73122 does inhibit phospholipase C beta in hepatocytes, complete inhibition of this enzyme in situ requires an intracellular concentration of U73122 higher than that achieved in the present experiments. Moreover, both U73122 and 'inactive' analogue U73433 have one or possibly two additional sites of action. These are likely to be the hepatocyte plasma membrane Ca2+ inflow channel protein (or a protein involved in the activation of this channel by the InsP3-sensitive intracellular Ca2+ store), and a protein involved in thapsigargin action.
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PMID:Evidence obtained using single hepatocytes for inhibition by the phospholipase C inhibitor U73122 of store-operated Ca2+ inflow. 776 79

The role of heterotrimeric GTP-binding proteins in the process of store-operated Ca2+ inflow in hepatocytes was investigated by testing the ability of pertussis toxin to inhibit thapsigargin- and 2,5-di-tert-butylhydroquinone (DBHQ)-induced bivalent cation inflow. Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited markedly inhibited rates of both Ca2+ and Mn2+ inflow when these were stimulated by vasopressin, angiotension II, epidermal growth factor, thapsigargin and DBHQ. Pertussis toxin had little effect on the basal intracellular free Ca2+ concentration ([Ca2+]i), basal rates of Ca2+ and Mn2+ inflow, the abilities of vasopressin, angiotensin II, thapsigargin and DBHQ to induce the release of Ca2+ from intracellular stores, and the maximum value of [Ca2+]i reached following agonist-induced release of Ca2+ from intracellular stores. It is concluded that store-operated Ca2+ inflow in hepatocytes employs a slowly ADP-ribosylated trimeric GTP-binding protein and is the physiological mechanism, or one of the physiological mechanisms, by which vasopressin and angiotensin stimulate plasma membrane Ca2+ inflow in this cell type.
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PMID:Evidence from studies with hepatocyte suspensions that store-operated Ca2+ inflow requires a pertussis toxin-sensitive trimeric G-protein. 798 Mar 92

The relationship between phospholipase D and C activation was studied in intact rat hepatocytes and rat liver plasma membranes. In intact hepatocytes, in the presence of ethanol, vasopressin, phorbol ester, and calcium independently stimulated phosphatidylethanol (PETH) formation, a specific marker of phospholipase D activity. Leupeptin (10-1500 microM) inhibited PETH formation induced by vasopressin, but was ineffective in response to phorbol ester or calcium. Leupeptin also inhibited the formation of inositol phosphates in intact cells in response to vasopressin. In liver plasma membranes, GTP[S] induced the production of phosphatidic acid and, in the presence of ethanol, PETH. Plasma membrane-associated phospholipase D did not require calcium and was insensitive to protein kinase C inhibitors. Leupeptin inhibited PETH formation in response to GTP[S]. The inhibition by leupeptin could be overcome by increasing the concentration of GTP[S]. In plasma membranes, the inhibitory effects of leupeptin on phospholipase D occurred at doses that far exceed those required to maximally inhibit proteolysis. These data highlight a central role for phospholipase C in the activation of phospholipase D, and a minor role for a direct G-protein activation. The findings also demonstrate a novel use of leupeptin as an inhibitor of phospholipases D and C, perhaps at the level of a G protein.
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PMID:Leupeptin inhibits phospholipases D and C activation in rat hepatocytes. 806 Oct 57


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