Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of glycoprotein GPIIb/IIIa (integrin alpha IIb beta 3) receptor occupancy by adenosine 5',1-thiotriphosphate (ATP alpha S), a competitive inhibitor of the ADP receptor, by fibrinogen, and by peptides containing the RGD (Arg-Gly-Asp) sequence as RGDW (Arg-Gly-Asp-Trp), RGDS (Arg-Gly-Asp-Ser), or the negative control RGGW (Arg-Gly-Gly-Trp) on human platelet physiological functions: aggregation, ATP secretion, and [Ca2+]in. As the presence of a nucleotide binding site on GPIIb alpha has been demonstrated in platelets [N. J. Greco, N. Yamamoto, B. W. Jackson, N. N. Tandon, M. Moos, and G. A. Jamieson (1991) J. Biol. Chem. 266, 13627-13633], we studied the effect of ATP alpha S, which specifically binds to this site, on platelet activation. We observed that ATP alpha S inhibited aggregation by thrombin, ADP, PMA, and ionophore A23187. Moreover, ATP alpha S dose dependently inhibited ATP secretion by ionophore A23187 and Ca2+ transients by thrombin and vasopressin in both the presence and absence of external Ca2+. Fibrinogen, although induced by a potentiation of platelet aggregation, inhibited ATP secretion and [Ca2+]in elevation induced by low thrombin concentrations or by vasopressin, interfering with both Ca2+ entry and Ca2+ release by the intracellular stores. RGD peptides, which specifically bind to GPIIb/IIIa, inhibited aggregation, secretion, and Ca2+ transients by thrombin, whereas the negative control RGGW did not exert any effect. We conclude that the occupancy of the GPIIb/IIIa receptor binding sites modulates platelet function by giving an inhibitory outside-in signal in platelets, particularly effective in platelets stimulated with low agonist doses. We suggest that ATP alpha S, fibrinogen, or RGD compounds, by interacting with GPIIb/IIIa receptor, prime some intracellular negative feedback mechanisms, which prevent further activation of circulating platelets by low-intensity stimuli and intravascular aggregation.
 ...
PMID:Human platelet activation is inhibited by the occupancy of glycoprotein IIb/IIIa receptor. 880 80

The involvement of protein kinase C (PKC) in vasopressin-induced effects on renal water reabsorption is still unresolved. Activation of PKC can be detected by its translocation from the cytosol (C) to the plasma membrane (PM). In LLC-PK1 cells, the redistribution of PKC alpha, a predominant isoform of PKC detected, was studied utilizing western blotting after stimulation with vasopressin. Vasopressin (100 mU/ml) failed to induce a translocation of PKC alpha from the C to the PM. By contrast, phorbol myristate acetate (PMA, 200 nM), a potent activator of PKC, induced a relocalization of PKC alpha from the C to the PM. After 2 hours of treatment of cells with PMA, PKC alpha was predominantly detected in the PM and absent from the C. These results suggest that the signal transduction pathway of vasopressin in LLC-PK1 cells does not involve PKC alpha activation and translocation.
 ...
PMID:Is protein kinase C alpha (PKC alpha) involved in vasopressin-induced effects on LLC-PK1 pig kidney cells? 882 10

1. We evaluated responses of peripheral resistance arterial smooth muscle to alpha 1-adrenoceptor stimulation in a rat model of heart failure in relation to neurohumoral changes, wall structure, receptor density and cellular calcium handling. 2. Plasma samples and third order mesenteric artery side-branches were obtained from Wistar rats after induction of left ventricular infarction (M1) or sham surgery. Vessels were denuded of endothelium, sympathectomized, depleted of neuropeptides, and mounted in a myograph for recording of isometric force development in response to calcium, agonist and high potassium. Also, the morphology of these preparations was determined. Separate vessel segments were used in radioligand binding assays with [1H]-prazosin. 3. At 1 week after MI, circulating plasma levels of adrenaline, angiotensin II, atrial natriuretic factor (ANF) and vasopressin were significantly elevated. At 5 weeks only a significant elevation of ANF persisted. 4. At 5 weeks after MI, the structure of the vessels and responsiveness to high potassium or Bay K 8466 (10(6) mol l-1) were not modified. Yet, at this stage, sensitivity to phenylephrine was increased (pD2: 6.24 +/- 0.04 vs 5.98 +/- 0.04 for controls) while maximal contractile responses to phenylephrine in the presence of 2.5 mmol l-1 calcium (2.26 +/- 0.28 vs 3.53 +/- 0.34 N m-1) and the sensitivity to calcium in the presence of phenylephrine (pD2: 2.81 +/- 0.22 vs 3.74 +/- 0.16) were reduced. Responses to the agonist in calcium-free solution and the calcium sensitivity in the presence of 125 mmol l-1 potassium or of phorbol myristate acetate (PMA, 10(-6) mol l-1) were not altered. 5. At 5 weeks after MI, the density of prazosin binding sites was not reduced (4.04 +/- 1.40 vs 2.29 +/- 0.21 fmol microgram-1 DNA in controls). 6. In conclusion, myocardial infarction leads in the rat to a reduction of contractile responses of mesenteric resistance arterial smooth muscle to alpha 1-adrenoceptor stimulation. This seems to involve impaired agonist-stimulated calcium influx.
 ...
PMID:Reduced responsiveness of rat mesenteric resistance artery smooth muscle to phenylephrine and calcium following myocardial infarction. 911 72

Ca2+ influx into cells in response to stimulation of various receptors was studied with Swiss 3T3 fibroblasts. The mechanisms involved were found to be so diverse that they were classified into four groups, Type I to IV. Type-I influx occurred, via pertussis toxin-susceptible G-proteins, immediately after internal Ca2+ mobilization by bradykinin, thrombin, endothelin, vasopressin or angiotensin II. Type-II influx induced by bombesin differed from Type I in its insusceptibility to pertussis toxin treatment. Ca2+ influx induced by prostaglandin E1, referred to as Type-III influx, was unique in that phospholipase C was apparently not activated without extracellular Ca2+, strongly suggesting that the Ca2+ influx preceded and was responsible for InsP3 generation and internal Ca2+ mobilization. More Ca2+ entered the cells more slowly via the Type-IV route opened by platelet-derived and other growth factors. These types of Ca2+ influx could be differentiated by their different susceptibilities to protein kinase C maximally activated by 1 h of exposure of cells to PMA, which inhibited phospholipase Cbeta coupled to receptors involved in Type-I and -II influx but did not inhibit growth-factor-receptor-coupled phospholipase Cgamma. Type-I and -II Ca2+ influxes, together with store-operated influx induced by thapsigargin, were not directly inhibited by exposure of cells to PMA, but Type-III and -IV influxes were completely inhibited. In addition, stimulation of receptors involved in Type-I and -IV Ca2+ influx, but not Type-II and -III influx, led to phospholipase A2 activation in the presence of extracellular Ca2+. Inhibition of Type-I and -IV Ca2+ influxes by their respective inhibitors, diltiazem and nifedipine, resulted in abolition of phospholipase A2 activation induced by the respective receptor agonists, in agreement with the notion that Ca2+ influx via these routes is responsible for receptor-mediated phospholipase A2 activation.
 ...
PMID:Differential routes of Ca2+ influx in Swiss 3T3 fibroblasts in response to receptor stimulation. 940 82

Cross-talk between the phospholipase C and adenylyl cyclase signalling pathways was investigated in Chinese hamster ovary (CHO) cells transfected with the V1a and V2 vasopressin receptors. Cell lines expressing V1a, V2, or both V1a and V2 receptors, were established and characterized. Stimulation of V2 receptors by vasopressin induced a dose-dependent increase in cAMP accumulation, whereas stimulation of V1a receptor resulted in an increase in intracellular calcium without any change in basal cAMP. The simultaneous stimulation of V2 and V1a receptors by vasopressin elicited an intracellular cAMP accumulation which was twice that induced by stimulation of V2 receptor alone with deamino-[d-Arg8]vasopressin. This potentiation between V1a and V2 receptors was mimicked by activation of protein kinase C (PKC) with PMA, and was suppressed when PKC activity was inhibited by bisindolylmaleimide. The potentiation was observed in the presence or absence of 1 mM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, implying that an alteration in cAMP hydrolysis was not involved. Vasopressin, as well as PMA, had no effect on the forskolin-induced cAMP accumulation, suggesting that PKC did not directly stimulate the cyclase activity. On the other hand, vasopressin, like PMA, potentiated the cAMP accumulation induced by cholera toxin, an activator of Galphas protein. These results suggest that, in CHO cells, vasopressin V1a receptor potentiates the cAMP accumulation induced by the V2 receptor through a PKC-dependent increase in the coupling between Gs protein and adenylyl cyclase.
 ...
PMID:Potentiation of receptor-mediated cAMP production: role in the cross-talk between vasopressin V1a and V2 receptor transduction pathways. 948 Sep 25

This study examines the involvement of hormones and neuromediators in the regulation of Na+, K+, Cl- cotransport in renal epithelial cells using Madin-Darby canine kidney cells with low transepithelial electrical resistance (194+/-47 Omega/cm2). In this cell line, Na+, K+, Cl- cotransport measured as bumetanide-sensitive 86Rb influx was inhibited up to 50-60% with agonists of P2-purinoceptors (ATP approximately ADP>UTP>AMP), slightly (15-30%) increased by activators of cAMP signaling (forskolin, 8-Br-cAMP) and was insensitive to activators of cGMP signaling (8-Br-cGMP, nitroprusside), EGF, angiotensin II, bradykinin, methacholine, propranolol, vasopressin, adenosine, dopamine and histamine. Thirty min of preincubation of MDCK cells with 0.1 microM PMA completely blocked the activity of Na+, K+, Cl- cotransport whereas down-regulation of this enzyme by 24 h of preincubation with 1 microM PMA activated Na+, K+, Cl- cotransport by 60% and abolished the effect of short-term treatment with PMA. Regulation of Na+, K+, Cl- cotransport by ATP was insensitive to down-regulation of PMA-sensitive isoforms of protein kinase C. In addition, an inhibitor of protein kinase activity, staurosporine, abolished the effect of 0.1 microM PMA but did not change inhibition of this carrier by ATP. Thus, these results show for the first time that P2-purinoceptors and PMA-sensitive isoforms of protein kinase C play a key role in the regulation of Na+, K+, Cl- cotransport in MDCK cells. These results also show that neither PMA- nor staurosporine-sensitive forms of protein kinase are involved in the inhibition of Na+, K+, Cl- cotransport by activators of P2-purinoceptors.
 ...
PMID:Complete inhibition of Na+, K+, Cl- cotransport in Madin-Darby canine kidney cells by PMA-sensitive protein kinase. 951 30

Physiological vasoconstrictor concentrations of Arg8-vasopressin (AVP, 10-100 pM) stimulate oscillations (spikes) in cytosolic free Ca2+ concentration ([Ca2+]i) in A7r5 rat vascular smooth muscle cells. These Ca2+ spikes are dependent on L-type voltage-sensitive Ca2+ channels and increase in frequency with increasing AVP concentration. The signal transduction pathway responsible for this effect was examined in fura-2-loaded A7r5 cell monolayers. The serine/threonine phosphatase inhibitor calyculin A (5 nM) sensitized A7r5 cells to AVP, resulting in the stimulation of Ca2+ spiking by 1-10 pM AVP. Calyculin A alone did not stimulate Ca2+ spiking. The protein kinase C (PKC) activator 4beta-phorbol 12-myristate 13-acetate (PMA, 100 pM to 200 nM), also stimulated Ca2+ spiking and this effect was additive with a submaximal concentration of AVP (50 pM). The PKC inhibitors Ro-31-8220 (1 microM) and calphostin C (250 nM) completely blocked the stimulation of Ca2+ spiking by either PMA or AVP. alpha, beta, gamma, delta, epsilon, zeta and &lamdda; isoforms of PKC were detected in A7r5 cells by Western blot analysis. Time-dependent redistribution of PKC-alpha, -delta and -epsilon isoforms between the membrane and cytosolic fractions occurred in response to 100 pM AVP. Pretreatment for 24 h with 1 microM PMA downregulated expression of PKC-alpha and -delta, but not PKC-epsilon, and prevented the Ca2+-spiking responses to either 1 nM PMA or 100 pM AVP. Neither the release of intracellular Ca2+ by 1 microM AVP nor the increase in [Ca2+]i in response to elevated extracellular [K+] was prevented by the PMA pretreatment. We conclude that PKC activation is a necessary step in the signal transduction pathway linking low concentrations of AVP to Ca2+ spiking in A7r5 cells.
 ...
PMID:Ca2+ signalling in rat vascular smooth muscle cells: a role for protein kinase C at physiological vasoconstrictor concentrations of vasopressin. 1079 Jan 61

A new cell line was derived from primary culture of rat choroid plexus (RCP) by immortalization with the TSOri minus adenovirus. The selected clone expressed vasopressin V1a receptors at a density of 64,000 sites per cell, and a K(d) of 7.2 nM. Addition of vasopressin to the RCP cells induced a transient calcium peak comparable to V1a receptor signalling in different expression systems. This [Ca(2+)](i) increase was dose-dependent with an EC(50) of 22 nM vasopressin. Similar [Ca(2+)](i) increase was elicited by addition of serotonin, angiotensin II, endothelin-1, and bradykinin. Heterologous desensitization of V1a receptor was observed in RCP cells exposed to the phorbol ester PMA or following stimulation of other receptors coupled to the phosphoinositide pathway. Positive immunolabelling with Factor VIII, Flt1 and CD 34 antibodies suggests that this new RCP cell line originated from endothelial cells of rat choroid plexus.
 ...
PMID:Vasopressin V1a receptor signaling in a rat choroid plexus cell line. 1096 65

Phospholipase D (PLD) is distributed widely in mammalian tissues where it is believed to play an important role in the regulation of cell functions and cell fate by a variety of extracellular signals. In this study, we used primary cultures of rabbit connecting tubule (CNT) and cortical collecting duct (CCD) cells, grown to confluence on a permeable support, to investigate the possible involvement of PLD in the mechanism of action of hormones that regulate Ca(2+) reabsorption. RT-PCR revealed the presence of transcripts of PLD1b and PLD2, but not PLD1a, in these cultures. Moreover, the expression of substantial amounts of PLD1 protein was demonstrated by Western blotting. To measure PLD activity, cells were labelled with [(3)H]myristic acid after which the PLD-catalysed formation of radiolabelled phosphatidylethanol ([(3)H]PtdEth) was measured in the presence of 1% (v/v) ethanol. Deamino-Cys,D-Arg(8)-vasopressin (dDAVP) and N(6)-cyclopentyladenosine (CPA), two potent stimulators of Ca(2+) transport across these monolayers, stimulated PLD activity as was indicated by a marked increase in [(3)H]PtdEth. Similarly, ATP, a potent inhibitor of dDAVP- and CPA-stimulated Ca(2+) transport, increased the formation of [(3)H]PtdEth. PLD activity was furthermore increased by 8Br-cAMP and following acute (30 min) stimulation of protein kinase C (PKC) with a phorbol ester (PMA). Chronic PMA treatment (120 h) to downregulate phorbol ester-sensitive PKC isoforms did not affect PLD activation by dDAVP, CPA and 8Br-cAMP, while markedly decreasing the effect of ATP and abolishing the effect of PMA. The PKC inhibitor chelerythrine significantly reduced PLD activation by dDAVP, CPA and 8Br-cAMP, without changing the effect of ATP. The inhibitor only partially reduced the effect of PMA. This study shows that Ca(2+) transporting cells of CNT and CCD contain a regulated PLD activity. The physiological relevance of this activity, which is not involved in Ca(2+) reabsorption, remains to be established.
 ...
PMID:Hormonal regulation of phospholipase D activity in Ca(2+) transporting cells of rabbit connecting tubule and cortical collecting duct. 1133 4

In renal collecting ducts, a vasopressin-induced cAMP increase results in the phosphorylation of aquaporin-2 (AQP2) water channels at Ser-256 and its redistribution from intracellular vesicles to the apical membrane. Hormones that activate protein kinase C (PKC) proteins counteract this process. To determine the role of the putative kinase sites in the trafficking and hormonal regulation of human AQP2, three putative casein kinase II (Ser-148, Ser-229, Thr-244), one PKC (Ser-231), and one protein kinase A (Ser-256) site were altered to mimic a constitutively non-phosphorylated/phosphorylated state and were expressed in Madin-Darby canine kidney cells. Except for Ser-256 mutants, seven correctly folded AQP2 kinase mutants trafficked as wild-type AQP2 to the apical membrane via forskolin-sensitive intracellular vesicles. With or without forskolin, AQP2-Ser-256A was localized in intracellular vesicles, whereas AQP2-S256D was localized in the apical membrane. Phorbol 12-myristate 13-acetate-induced PKC activation following forskolin treatment resulted in vesicular distribution of all AQP2 kinase mutants, while all were still phosphorylated at Ser-256. Our data indicate that in collecting duct cells, AQP2 trafficking to vasopressin-sensitive vesicles is phosphorylation-independent, that phosphorylation of Ser-256 is necessary and sufficient for expression of AQP2 in the apical membrane, and that PMA-induced PKC-mediated endocytosis of AQP2 is independent of the AQP2 phosphorylation state.
 ...
PMID:The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel. 1219 85


<< Previous 1 2 3 4 Next >>