UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E2 (PGE2) was found to bind specifically, reversibly, and in a protein-dependent manner to a single class of high affinity (KD approximately equal to 20 nM) binding sites in membranes prepared from canine renal outer medulla. PGE2 binding activity was solubilized from these membranes in a stable form (t1/2 greater than 14 days) in the absence of ligand in 75% yields using digitonin. The characteristics of PGE2 binding to membranes and solubilized protein were similar with respect to pH dependence, KD for PGE2, and order of potency of prostaglandins (PGE2 approximately PGE1 greater than PGF2 alpha greater than PGD2) in inhibiting the binding of [3H]PGE2. Importantly, the extents of binding of PGE2 to membranes and to a solubilized preparation partially purified by chromatography on wheat germ agglutinin-Affi-Gel 10 were both increased about 2-fold by GDP and GTP and its analogs. Treatment of the digitonin-solubilized PGE2 binding activity with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) rendered the binding activity insensitive to stimulation by GTP and decreased the apparent molecular weight of the peak of PGE2 binding activity from about 175,000 to about 65,000. These results suggest that the PGE2 binding activity resides in a protein which is tightly associated with, but distinct from, a guanine nucleotide regulatory (N) protein. PGE2 (greater than or equal to 10 nM) was found to stimulate GTPase activity of renal outer medullary membranes, and this stimulation was eliminated by pretreatment of membranes with pertussis toxin and NAD, but not cholera toxin and NAD. Treatment of both particulate and solubilized preparations of PGE2 binding activity with pertussis toxin plus NAD also eliminated the ability of GTP to stimulate PGE2 binding. This evidence indicates that it is the inhibitory guanine nucleotide regulatory protein, Ni, with which the PGE2 binding activity is associated. Thus, this PGE2 binding activity is an inhibitory PGE2 receptor, quite possibly one that mediates inhibition of vasopressin-induced cAMP formation in the medullary thick ascending limb and/or collecting tubule of the kidney.
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PMID:Association of a solubilized prostaglandin E2 receptor from renal medulla with a pertussis toxin-reactive guanine nucleotide regulatory protein. 287 97

A guanine nucleotide regulatory protein may be involved in vasopressin-receptor-mediated polyphosphoinositide breakdown in rat liver. Therefore we examined the effects of the non-hydrolysable guanine nucleotide guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG) on [3H]vasopressin ([3H]AVP) binding to hepatic plasma membranes and detergent extracts. [3H]AVP bound to a single set of high-affinity binding sites in membranes. Addition of p[NH]ppG decreased the affinity of receptor binding without altering the maximal binding capacity. The rate of dissociation of [3H]AVP from membrane-bound receptors was also enhanced by p[NH]ppG. Solubilization of [3H]AVP-prelabelled membranes with dodecyl beta-D-maltoside resulted in a [3H]AVP-receptor complex that was unstable in solution. Incubation of these extracts for 5 min at 30 degrees C resulted in a 40% loss of bound [3H]AVP, whereas in the presence of p[NH]ppG there was a 54% loss. However, when membranes were prelabelled with [3H]AVP and p[NH]ppG and then solubilized, the resulting hormone-receptor complex was still temperature-labile but insensitive to the further addition of p[NH]ppG. The molecular size of soluble vasopressin receptors was estimated by gel filtration. The [3H]AVP-receptor complex was eluted as a single peak with an apparent molecular size of 258 kDa. However, no peak was detected when solubilized extract was made from membranes prelabelled with [3H]AVP and p[NH]ppG, suggesting that this receptor complex had dissociated during chromatography. It is possible therefore that the high-Mr complex contains the hormone, its receptor and a guanine nucleotide binding protein.
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PMID:Guanine nucleotide regulation of [3H]vasopressin binding to liver plasma membranes and solubilized receptors. Evidence for the involvement of a guanine nucleotide regulatory protein. 294 38

The mode of phospholipase C activation initiated with platelet-derived growth factor (PDGF) has been studied in comparison with that initiated with vasopressin and bombesin in a rat fibroblast line, WFB. Stimulation of WFB cells by PDGF, vasopressin, and bombesin elicites rapid hydrolysis of polyphosphoinositides and an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i). On stimulation by PDGF, there was a lag period of about 10 s before an increase in [Ca2+]i. No measurable lag period was observed in the [Ca2+]i response induced by vasopressin or bombesin. Pretreatment of WFB cells with phorbol 12-myristate 13-acetate profoundly inhibited inositol phosphate formation evoked by vasopressin and bombesin, but enhanced to some extent inositol phosphate formation stimulated by PDGF. In membranes prepared from WFB cells, GTP markedly augmented inositol polyphosphate formation induced by vasopressin and bombesin. It was not successful in showing the PDGF-stimulated formation of inositol phosphates in the membrane preparation. The effects of GTP, guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) on polyphosphoinositide hydrolysis stimulated by growth factors were studied in WFB cells made permeable to nucleotides by treatment with either saponin or Pseudomonas aeruginosa cytotoxin. PDGF, vasopressin, and bombesin elicited inositol phosphate production in the permeabilized WFB cells in the absence of added GTP. GDP beta S, a competitive inhibitor of GTP-binding proteins (G-proteins), markedly reduced the bombesin- and vasopressin-stimulated production of inositol phosphates. However, the PDGF-stimulated production of inositol phosphates was not affected by the addition of GDP beta S. GTP gamma S, an agonist of G-proteins, largely enhanced the vasopressin- and bombesin-stimulated hydrolysis of inositol lipids when added at 10-100 microM. In the presence of GTP gamma S, the PDGF-stimulated hydrolysis of inositol lipids was not enhanced, but was reduced: 100 microM GTP gamma S reduced the stimulated hydrolysis to about a half of the control level. Only GTP gamma S, and no other nucleoside triphosphates, was found to have these effects. Activation of G-proteins in WFB cells by fluoroaluminate resulted in the inhibition of inositol phosphate production elicited with not only PDGF, but also with vasopressin and bombesin. These results indicate that a G-protein couples vasopressin and bombesin receptors to the activation of phospholipase C. Moreover, these results suggest that coupling of the PDGF receptor to phospholipase C is not mediated through a G-protein.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathway of phospholipase C activation initiated with platelet-derived growth factor is different from that initiated with vasopressin and bombesin. 304 15

In rat renal medullary membranes, we have examined modulatory effects of guanine nucleotides on binding of arginine8 vasopressin (AVP) to its receptor. Equilibrium binding studies analyzed by an iterative curve fitting program revealed an interaction of (3H) AVP with a single class of binding sites with a dissociation constant of 1.4 +/- 0.2 nM and a binding site concentration of 201 +/- 37 fmol/mg protein (n = 6). With the addition of 100 microM guanylyl-imidodiphosphate (Gpp(NH)p), the binding site concentration was significantly (p less than 0.01) reduced to 151 +/- 36 fmol/mg protein with no change in receptor affinity. The nonhydrolyzable analogues, guanosine-5'-0-(3-thiophosphate) and Gpp(NH)p were the most potent inhibitors of (3H) AVP binding. Guanosine 5'-triphosphate and guanosine-5'-diphosphate were both relatively poor inhibitors. Guanosine-5'-monophosphate and adenosine 5'-triphosphate did not inhibit (3H) AVP binding at concentrations up to 100 microM. Furthermore, 100 microM Gpp(NH)p accelerated the dissociation of (3H) AVP from the receptor. We conclude that guanine nucleotides are important modulators of AVP binding to the V2 receptor subtype in the renal medulla.
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PMID:Regulation of (3H) arginine8 vasopressin binding to the rat renal medulla by guanine nucleotides. 352 88

Radiation inactivation is used to probe the sequence of subunit interactions involved in the activation of adenylate cyclase by vasopressin in cultured renal epithelial cells (LLC-PK1) based on our previous analysis of the radiation inactivation of multimeric enzymes [Verkman et al., Am. J. Physiol. 250 (Cell Physiol. 19): C103-C114, 1986]. For basal adenylate cyclase activity, a concave downward ln(activity) vs. dose relation was observed with limiting slope corresponding to a molecular weight of (169-196) X 10(3). Similar results were obtained with NaF. In contrast, addition of vasopressin, guanylyl imidodiphosphate, or forskolin resulted in transition to a linear ln(activity) vs. dose relation with a slope corresponding to a molecular weight similar to that observed for basal activity. These findings were incorporated into a cyclic dissociation model for the hormonal activation of adenylate cyclase (graph see text) where H is hormone, R is receptor, C is catalytic unit, alpha and beta are subunits of guanyl nucleotide-regulatory protein (G), GTP is guanosine triphosphate, and GDP is guanosine diphosphate. The addition of H favors the dissociation of G into alpha and beta subunits by providing a rapid pathway for addition of GTP to dissociated alpha subunits. The observed target size of the active enzyme species formed corresponds to the composite molecular weights of alpha GTP with C. This model consolidates the radiation inactivation findings as well as the known biochemical characteristics for adenylate cyclase.
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PMID:Evidence for vasopressin activation of adenylate cyclase by subunit dissociation. 394 2

Exposure of human platelets to 10 discharges from a 4.5 microF capacitor charged at 3 kV permitted isolation of a stable preparation of permeabilized platelets that, after equilibration with Ca2+ buffers (pCa less than 6) for 15 min at O degrees C, secreted 5-hydroxytryptamine (5-HT) at 25 degrees C. Thrombin enhanced the sensitivity to Ca2+ of the secretion of 5-HT by about 10-fold, whereas Arg -vasopressin and the prostaglandin endoperoxide analogue, U-46619, increased sensitivity to Ca2+ by 3 to 4-fold. This action of thrombin was associated with stimulation of diacylglycerol formation, a marked increase in phosphorylation of protein P47 and a smaller increase in phosphorylation of the P-light chain of myosin. Thrombin exerted these effects at a [Ca2+ free] of 0.1 microM, suggesting that the receptor-activated breakdown of platelet phosphoinositides to diacylglycerol may not require prior Ca2+ mobilization in intact platelets. In both the presence and absence of thrombin, a higher [Ca2+ free] was required for optimal secretion than for maximal phosphorylation of P47 and myosin light-chain, indicating that Ca2+ and possibly diacylglycerol have roles in the secretory mechanism additional to activation of the enzymes that phosphorylate these proteins. Stable GTP analogues such as guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S), and to a lesser extent GTP itself, enhanced the Ca2+ sensitivity of the secretion of 5-HT from permeabilized platelets. Moreover, GTP potentiated the stimulatory action of thrombin. These effects of GTP gamma S and GTP were associated with increased diacylglycerol formation and were inhibited by guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) suggesting that a GTP-binding protein may play a role in the receptor-activated breakdown of phosphoinositides. However, as GDP beta S did not inhibit the potentiation of secretion caused by thrombin alone, a GTP-independent pathway of platelet activation may also exist.
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PMID:Receptor-induced diacylglycerol formation in permeabilized platelets; possible role for a GTP-binding protein. 609 73

In the present study, we examined the effects of guanine nucleotides on vasopressin-induced osmotic water flow and sodium transport in the 14-h preincubated frog bladder. We also examined the effects of the adenylate cyclase-cyclic AMP and cyclic AMP-dependent protein kinase system in the bladder's epithelial cells. Gpp(NH)p significantly enhanced vasopressin-induced water flow while it did not affect cyclic AMP-induced water flow. However, Gpp(NH)p did not enhance the vasopressin-induced increment of sodium transport across the frog bladder. The adenylate cyclase activity of the crude homogenate was enhanced by vasopressin, Gpp(NH)p and NaF. The effects of Gpp(NH)p and vasopressin, at their maximum doses, on the enzyme activities were additive, while other combinations were not. Specific Gpp(NH)p binding sites were found in the pellet fraction after 2,400 X g centrifugation. No direct effect on the protein kinase activity was observed in the presence of 10(-6) M nucleotides, such as GTP, GDP, GMP, CTP, UTP, ITP and Gpp(NH)p. Cyclic AMP stimulated the phosphorylation of discrete protein bands, however, Gpp(NH)p did not influence cyclic AMP-dependent protein phosphorylation of crude homogenate of the bladder's epithelial cells. These results suggest the guanine nucleotides stimulate the vasopressin-induced osmotic water flow in frog bladder by enhancing the vasopressin-mediated adenylate cyclase activity, so that accumulated cyclic AMP might activate cyclic AMP-dependent protein kinase.
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PMID:Effects of guanine nucleotides on vasopressin-induced water flow and sodium transport of the frog bladder. 660 7

The effects of arginine-vasotocin and nucleotides on the steady-state kinetics of the adenylate cyclase activity in the epithelial cell membranes of the bullfrog (Rana catesbiana) bladder were studied. Arginine-vasotocin stimulated adenylate cyclase more effectively than oxytocin or arginine-vasopressin, with respect to both the maximal hormonal activation ratio relative to basal, and the hormone concentration yielding a half-maximal response (apparent Km). Arginine-vasotocin, GTP and its analogue guanyl-5'-yl imidodiphosphate (Gpp(NH)p) increased the Vmax of the basal adenylate cyclase activity, but showed no effect of the apparent Km of the system for ATP. In addition, Gpp(NH)p enhanced the arginine-vasotocin-stimulated adenylate cyclase activity, further increasing the Vmax, while GTP showed no statistically significant effect. Dual effects of GDP were apparent: it was stimulatory at 1 x 10(-5) mol/l and inhibitory at 1 x 10(-3) mol/l, on both the basal and the arginine-vasotocin-stimulated adenylate cyclase activity. Guanosine 5'-monophosphate, CTP, UTP and ITP showed no apparent effect on the enzyme activity. Sodium fluoride acted in the same manner as GTP on the adenylate cyclase system, increasing only basal activity. Adenylate cyclase activities exhibited pH optima that were less distinct in the presence than in the absence of Gpp(NH)p. The Arrhenius plot of the temperature experiment showed that a high-energy step was involved for activation by Gpp(NH)p or arginine-vasotocin. When the relative activation ratios by arginine-vasotocin at different ATP concentrations were studied, a distinct activation optimum was shown at 2.5 x 10(-4) mol ATP/l, either in the absence or presence of Gpp(NH)p. The possibility that GTP, GDP nd ATP play a regulatory role in the epithelial cells of the bullfrog bladder by adjusting the responsiveness of the system to a natural hormone, arginine-vasotocin, is discussed.
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PMID:Stimulatory and inhibitory effects of guanine nucleotides on arginine-vasotocin-sensitive adenylate cyclase in the epithelial cell membranes of the bullfrog bladder. 660 97

The effect of (R,S)-(3,4-dihydro 6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl- N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908), a cation channel blocker in HL-60 promyeloblasts, was studied in the A7r5 smooth muscle cell line from rat thoracic aorta, using the whole-cell patch-clamp technique. At a holding potential of -60 mV, application of vasopressin induced a nonselective cation conductance in voltage-clamped A7r5 cells. The current-voltage relation was linear, and currents reversed close to 0 mV regardless of the chloride gradient. The activation of the nonselective cation conductance by vasopressin was not affected by dialysing cells with Ca(2+)-free internal solution. LOE 908 blocked this current in a concentration-dependent manner with an IC50 of 560 nM, whereas dihydropyridine-sensitive Ba2+ current through voltage-dependent Ca2+ channels was blocked with an IC50 of 28 microM. Another organic blocker of receptor-mediated Ca2+ entry, 1-beta-[3-(4-methoxyphenyl)-propoxy]-4-methoxyphenethyl-1H-imidazole hydrochloride (SK&F 96365), blocked both, the vasopressin-induced nonselective conductance and the voltage-activated Ba2+ current with similar IC50 values of 13 microM and 8 microM, respectively. The rank order of potency of inorganic blockers on the vasopressin-induced inward current was Gd3+ > La3+ > Cd2+. Vasopressin-induced non-selective cation current was also observed in pertussis toxin-pretreated A7r5 cells but was completely abolished after infusion of the GDP analogue, guanosine 5'-O-[3-thio]diphosphate, from the patch pipette. Furthermore, vasopressin induced a transient outward current, suggesting a Ca(2+)-activated K(+)-current, which overlapped with the nonselective cation conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The isoquinoline derivative LOE 908 selectively blocks vasopressin-activated nonselective cation currents in A7r5 aortic smooth muscle cells. 751 40

To examine the effect of isoproterenol on Cl- current and its signal transduction pathway in beta-intercalated cells (beta-IC cell), peanut agglutinin (PNA) positive cells in culture were studied by the whole-cell clamp technique. We identified these cells as beta-IC cells by PNA-binding, cell alkalinization induced by Cl- free in the superfusate, and an increase in intracellular cAMP concentration by isoproterenol, but not by vasopressin. Application of isoproterenol in the voltage-clamp mode induced an activation of Cl- current in a dose-dependent fashion and its threshold concentration was in the order of 0.01 microM and ED50 was about 0.1 microM. This effect of isoproterenol was inhibited by atenolol, a beta-adrenergic blocker. Either extracellular application of forskolin or intracellular application of cAMP mimicked the action of isoproterenol. In the presence of forskolin or cAMP, isoproterenol caused little further activation of Cl- current. A synthetic inhibitor of protein kinase A (5-24 amide) inhibited the Cl- -channel activation by isoproterenol. Isoproterenol failed to activate the current in the presence of intracellular GDP beta S. By contrast, intracellular application of GTP gamma S rendered irreversible the Cl- -channel activation by brief exposure to isoproterenol. The present studies provide direct evidence that in the PNA-binding cell, probably the beta-IC cell, the stimulation of beta-adrenoceptor activates Cl- current through the signal transduction system involving G-protein, adenylate cyclase, cAMP, and protein kinase A.
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PMID:Isoproterenol stimulates Cl- current by a Gs protein-mediated process in beta-intercalated cells isolated from rabbit kidney. 810 76

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