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)

Vasopressin and bradykinin bind to receptors coupled to GTP-binding proteins and rapidly induce polyphosphoinositide breakdown leading to Ca2+ mobilization and activation of protein kinase C. Both peptides are known to induce mitogenesis in the presence of growth factors that act through receptors with intrinsic tyrosine kinase activity. Surprisingly, addition of a combination of vasopressin and bradykinin to Swiss 3T3 cells synergistically stimulates DNA synthesis in the absence of any other growth factors. This effect is induced at nanomolar concentrations of the peptides and could be inhibited by addition of specific receptor antagonists or broad spectrum neuropeptide antagonists. Bradykinin, which stimulates transient activation of protein kinase C, induces DNA synthesis in synergy with substances that cause long-term activation of protein kinase C, like vasopressin or phorbol 12,13-dibutyrate. Down-regulation of protein kinase C inhibited the induction of mitogenesis by the combination of vasopressin and bradykinin, thus demonstrating the importance of long-term activation of this enzyme for DNA synthesis. Analysis of tyrosine phosphorylated proteins of M(r) = 110,000-130,000 and M(r) = 70,000-80,000 revealed a biphasic response after stimulation with bradykinin, whereas the response induced by vasopressin declined after the initial maximum. The combination of bradykinin with vasopressin caused an enhanced and prolonged increase in tyrosine phosphorylation of these proteins as compared with the individual peptides. Inhibition of tyrosine phosphorylation by tyrphostin was paralleled by inhibition of DNA synthesis. Together, these results demonstrate synergistic stimulation of DNA synthesis by bradykinin and vasopressin via prolonged stimulation of multiple signaling pathways and imply that the interactive effects of Ca(2+)-mobilizing peptides on mitogenesis may be more general than previously thought.
 ...
PMID:Synergistic stimulation of DNA synthesis by bradykinin and vasopressin in Swiss 3T3 cells. 807 88

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.
 ...
PMID:Isoproterenol stimulates Cl- current by a Gs protein-mediated process in beta-intercalated cells isolated from rabbit kidney. 810 76

The activation properties of inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ stores in permeabilized and intact hepatocytes were investigated by monitoring Mn2+ quench of fura-2 compartmentalized within these stores, as Mn2+ passed through InsP3-activated channels in a retrograde manner. In cells permeabilized in suspension the InsP3-sensitive pool size was dependent on InsP3 dose, and there was a large unresponsive compartment. By contrast, essentially all of the compartmentalized dye was accessible following activation of a small fraction of the InsP3 receptors in carefully permeabilized attached cells. After loading the cytosol of intact hepatocytes with Mn2+, both submaximal and maximal vasopressin doses caused complete quench of the entire intracellular pool of compartmentalized fura-2. Vasopressin-induced Mn2+ quench occurred in a stepwise manner at doses that gave cytosolic Ca2+ oscillations, reflecting periodic opening of intracellular Ca2+ channels. Pretreatment with thapsigargin to eliminate feedback effects of Ca2+ fluxes converted the steps to a continuous quench. The data suggest that Ca2+ stores in attached permeabilized and intact hepatocytes are luminally connected, making the entire store accessible to InsP3. In cells permeabilized in suspension, GTP increased InsP3-sensitive pool size, and this effect was inhibited by cytochalasin B. GTP did not change the initial rate of Mn2+ quench but increased the proportion of slowly accessible stores in the InsP3-sensitive compartment, apparently by recruitment of InsP3-insensitive stores. Preincubation on ice or with cytoskeletal inhibitors dissociated slowly accessible compartments from the InsP3-sensitive stores in both intact and subsequently permeabilized attached hepatocytes. Addition of GTP to permeabilized cells reversed this disruption of store continuity. It is suggested that GTP- and cytoskeleton-dependent luminal communication between Ca2+ stores is an important determinant of function, which could modulate the availability of Ca2+ for release.
 ...
PMID:Luminal communication between intracellular calcium stores modulated by GTP and the cytoskeleton. 814 9

The roles of heterotrimeric GTP-binding regulatory proteins (G-proteins) and inositol polyphosphates in the mechanism by which vasopressin stimulates Ca2+ inflow in hepatocytes were investigated by using single cells loaded with fura2 by microinjection. Vasopressin-stimulated Ca2+ inflow was mimicked by microinjection of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) or guanosine 5'-[beta gamma-imido]triphosphate to the cells, but not adenosine 5'-[gamma-thio]triphosphate (ATP[S]) or guanosine 5'-[beta-thio]diphosphate (GDP[S]). Extracellular Gd3+ (5 microM) inhibited both vasopressin- and GTP[S]-stimulated Ca2+ inflow. GDP[S], but not GMP, administered to hepatocytes by microinjection, completely inhibited vasopressin-stimulated Ca2+ inflow and partially inhibited vasopressin-induced release of Ca2+ from intracellular stores. The microinjection of pertussis toxin had no effect either on the release of Ca2+ from intracellular stores or on Ca2+ inflow induced by vasopressin, but completely inhibited changes in these processes induced by epidermal growth factor (EGF). Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited no vasopressin- or GTP[S]-stimulated Ca2+ inflow, whereas the vasopressin-stimulated release of Ca2+ from intracellular stores was similar to that observed for control cells. Heparin or ATP[S] inhibited, or delayed the onset of, both vasopressin-induced release of Ca2+ from intracellular stores and vasopressin-stimulated Ca2+ inflow. Vasopressin-induced oscillations in intracellular [Ca2+] were observed in some heparin-treated cells. It is concluded that the stimulation by vasopressin of Ca2+ inflow to hepatocytes requires inositol 1,4,5-trisphosphate (InsP3) and, by implication, the pertussis-toxin-insensitive G-protein required for the activation of phospholipase C beta [Taylor, Chae, Rhee and Exton (1991) Nature (London) 350, 516-518], and another G-protein which is slowly ADP-ribosylated by pertussis toxin and acts between InsP3 and the putative plasma-membrane Ca2+ channel. EGF-stimulated Ca2+ inflow involves at least one G-protein which is rapidly ADP-ribosylated and is most likely required for InsP3 formation.
 ...
PMID:A slowly ADP-ribosylated pertussis-toxin-sensitive GTP-binding regulatory protein is required for vasopressin-stimulated Ca2+ inflow in hepatocytes. 817

We previously reported that pertussis toxin (PTX) had little effect on arginine vasopressin-induced formation of inositol trisphosphate (IP3) in rat aortic smooth muscle cells [Kondo et al.: Biochemical and Biophysical Research Communications 161:677-682, 1989]. In the present study, we investigated the mechanism of vasopressin-induced arachidonic acid release in rat aortic smooth muscle cells. Vasopressin stimulated both the release of arachidonic acid and the formation of IP3 dose dependently in the range between 10 pM and 1 microM. The effect of vasopressin on arachidonic acid release was more potent than that on the formation of IP3. Quinacrine, a phospholipase A2 inhibitor, significantly suppressed the vasopressin-induced arachidonic acid release but had little effect on the formation of inositol phosphates. NaF, a GTP-binding protein activator, mimicked vasopressin by stimulating the arachidonic acid release. The arachidonic acid release stimulated by a combination of vasopressin and NaF was not additive. PTX partially but significantly suppressed the vasopressin-induced arachidonic acid release. In the cell membranes, PTX catalyzed ADP-ribosylation of a protein with an M(r) of about 40,000. Pretreatment of membranes with 0.1 microM vasopressin in the presence of 2.5 mM MgCl2 and 100 microM GTP markedly attenuated this PTX-catalyzed ADP-ribosylation of the protein in a time-dependent manner. These results strongly suggest that PTX-sensitive GTP-binding protein is involved in the coupling of vasopressin receptor to phospholipase A2 in primary cultured rat aortic smooth muscle cells.
 ...
PMID:Vasopressin induces arachidonic acid release through pertussis toxin-sensitive GTP-binding protein in aortic smooth muscle cells: independence from phosphoinositide hydrolysis. 822 89

We have demonstrated in liver from male rats that both endothelin A (ETA) and ETB receptors coexist in equal proportion and that ETA receptors mediate a calcium-dependent activation of glycogenolysis. We describe here a sex difference in endothelin action in hepatocytes because, in female rats, 80% of the ET receptors are of ETB type and, accordingly, activation of glycogenolysis is an ETB-mediated process (EC50 = 0.03 pM). ET-1 stimulation of glycogenolysis in female rats was consecutive to activation of phosphatidylinositol 4,5-bisphosphate hydrolysis (EC50 = 0.03 pM) and to inhibition of the calcium extrusion pump (IC50 = 0.03 pM) in plasma membranes, with ET-1 approximately sarafotoxin S6C approximately ET-3. Endothelin regulation of each effector was potentiated by GTP gamma S. ET-1 did not stimulate adenylyl cyclase activity. To identify the nature of the guanine nucleotide regulatory proteins (G protein(s)) coupling ETB receptors to each effector, we used antibodies against the COOH terminus of different G protein alpha subunits. Antibodies reactive with Gs alpha (RM) blocked ET-1 inhibition of the calcium pump, while they did not affect ET-1 stimulation of phospholipase C. Antibodies reactive with Gq alpha (QL) dose-dependently antagonized stimulation of phospholipase C by ET-1 and vasopressin, without affecting ET-1 inhibition of the calcium pump. Antibodies reactive with Gi1 alpha/Gi2 alpha (AS) had no effect on either system. We conclude that the calcium signal provoked by endothelins in hepatocyte is not only consecutive to activation of phospholipase C but also to inhibition of the plasma membrane calcium pump, each effector being coupled to ETB receptors by different G proteins, Gq, and Gs.
 ...
PMID:Coupling of endothelin B receptors to the calcium pump and phospholipase C via Gs and Gq in rat liver. 829 32

Freshly isolated rat hepatocytes, loaded with the Ca2+ probe Fluo-3, responded to homologous pancreastatin with a sudden increase in free cytosolic Ca2+ ([Ca2+]i) as well as glucose release. Addition of rat pancreastatin (0.1 microM) to hepatocytes resulted in an increase in [Ca2+]i from 150 nM to 700 nM, which declined back to nearly basal values within 2-3 min. Half-maximal and maximal effects were observed at 0.3 and 100 nM pancreastatin respectively. The increase in [Ca2+]i induced by vasopressin and noradrenaline was very similar in extent (from 150 to 800 nM) to that produced by pancreastatin. Neither the alpha 1-adrenergic blocker prazosin nor the vasopressin antagonist V1 modified the increase in [Ca2+]i induced by pancreastatin. Pig pancreastatin and its 33-49 C-terminal fragment produced about 65 and 75% of the effect of homologous pancreastatin respectively. Glucose production correlated with changes in [Ca2+]i in the same order of potency: vasopressin > rat pancreastatin > pig 33-49 pancreastatin > pig 1-49 pancreastatin. The effect of pancreastatin on [Ca2+]i was decreased by 50% when Ca2+ was omitted from the medium, and totally abolished when hepatocytes were depleted of internal Ca2+ stores by preincubation without Ca2+ and with 2 mM EGTA. When hepatocytes were preincubated for 5 min with PMA, the effects of ATP and noradrenaline were prevented, and those of vasopressin and pancreastatin remained unchanged. The pretreatment of hepatocytes with pertussis toxin diminished the response to pancreastatin and vasopressin. These results suggest that pancreastatin is a new Ca(2+)-mobilizing glycogenolytic hormone acting through a specific receptor which may involve both pertussis-toxin-sensitive and -insensitive GTP-binding regulatory proteins.
 ...
PMID:Pancreastatin increases free cytosolic Ca2+ in rat hepatocytes, involving both pertussis-toxin-sensitive and -insensitive mechanisms. 837 59

We studied the cytoplasmic and nuclear signaling pathways of V1-vascular AVP receptors of human platelets, primary cultures of renal glomerular mesangial cells, and established cultures of the A7r5 aortic smooth muscle cell line. The immediate transmembrane signals are triggered by the formation of ligand-receptor complexes as illustrated by binding experiments with [3H]AVP (Kd = 2.50 nM), d(CH2)5Tyr(Me)AVP (Kd = 0.62 nM), the linear V1 antagonist phenylacetyl-D-Tyr(Et)-Phe-Val-Asn-Lys-Pro-[125I]Tyr-NH2 (Kd = 1.42 nM) or by fluorescence experiments with linear antagonists like phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 coupled to biotin and made fluorescent by labeling with tetramethylrhodamine-avidin. We used several approaches (radioreceptor binding, radioactive labeling, autoradiographic, enzymatic, photoaffinity labeling, and immunoblotting procedures) to identify the guanine nucleotide regulatory protein coupled to V1-vascular vasopressin receptors. AVP-stimulated GTPase activity of human platelet membranes was blocked by pretreatment with antibodies specific for the C-terminal of the newly described Gq alpha protein. In the presence of MgCl2, AVP increased labeling by the photoreactive GTP analog [alpha-32P]azidoanilido GTP of a platelet membrane protein of apparent molecular mass of 42 kDa. AVP effect was reversed by the specific V1-vascular antagonist d(CH2)5Tyr(Me)AVP and labeling was completely abolished by GTP gamma s.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytoplasmic and nuclear signaling pathways of V1-vascular vasopressin receptors. 851 70

We have characterized a specific binding site for angiotensin IV on bovine aortic endothelial cell membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.71; average of two experiments that yielded values of 0.71 and 0.72 nM). The binding site is saturable and relatively abundant with a maximal binding capacity of 0.59 pmol/mg protein (average of two experiments that yielded values of 0.39 and 0.78 pmol/mg of protein). Non-equilibrium kinetic analyses at 37 degree C revealed a calculated Kd of 59 pM (average of two experiments that yielded values of 67 and 50 pM). The binding site displays a high affinity for angiotensin receptors AT1 or AT2. An analysis of specificity showed that the binding site displays a high affinity for angiotensin IV, low affinities for angiotensin II, [Sar1, Val5, Ala8]angiotensin II and does not recognize L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'-(1 H-tetrazole-5-yl)[1,1'-biphenyl]-4-yl)methyl]-3H-imidazo[4, 5-beta]pyridine H2O) and PD 123319 (1-[4-dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl) 4,5,6,7-tetrahydro-1 H-imidazo[4,5-c]pyridine-6-carboxylic acid). A few unrelated hormones (bradykinin, [Arg8] vasopressin, endothelin-1, atrial natriuretic factor, isoproterenol and adrenocorticotropic hormone) were unable to inhibit any 125I-angiotensin IV binding. The affinities of different structural analogues of angiotensin IV revealed that the N-terminal position is critical for receptor recognition and the C-terminal proline is also important. GTP gamma S and polyvinyl sulfate did not affect the binding, suggesting that the receptor is not coupled to a G-protein. The divalent cations Mg2+ and Ca2+ were shown to diminish the binding of 125I-angiotensin IV. Cross-linking of 125I-angiotensin IV to bovine aortic endothelial cell membranes in the presence of disuccinimidyl suberate, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a major band of 186 +/- 12 kDa. The presence in high concentration of this angiotensin binding site on aortic endothelial cells suggest the existence of a novel mechanism involved in the control of vascular tone or vascular permeability.
 ...
PMID:Characterization of a binding site for angiotensin IV on bovine aortic endothelial cells. 856 70

Some hormones exert their action by inducing a rise in cytosolic calcium [Ca2+]i (calcium signal), and therefore, a blunting in hormone-induced calcium signal would engender resistance to the action of the hormone. Chronic renal failure (CRF) is associated with resistance to the action of a variety of hormones, a rise in [Ca2+]i and decrease in the amount of mRNA of one hormone receptor, the PTH-PTHrP receptor. We examined the calcium-signal induced by PTH, angiotensin II, vasopressin and glucagon in hepatocytes from CRF animals, evaluated the effect of the basal level [Ca2+]i on the calcium signal and explored the effect of [Ca2+]i on the mRNA of the receptors of these agonists. Hepatocytes from CRF rats have elevated basal levels of [Ca2+]i and display significantly reduced calcium signals induced by all these hormones, while the calcium signals were normal in PTX-CRF animals and those treated with verapamil both of which have normal levels of [Ca2+]i despite CRF. The calcium signals induced by dibutyryl cyclic AMP and G protein activator (GTP gamma S) were normal in hepatocytes from CRF animals despite the high levels of [Ca2+]i. Northern blotting experiments revealed that the levels of the mRNA of the receptors of PTH-PTHrP, angiotensin II and vasopressin were significantly reduced in hepatocytes from CRF animals but PTX-CRF rats and those treated with verapamil had either significantly greater or even normal amounts of the mRNA of these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Impaired agonist-induced calcium signaling in hepatocytes from chronic renal failure rats. 856 95


<< Previous 1 2 3 4 5 6 7 8 9 10