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)

Early signals elicited after membrane receptor binding of agonists, the transmembrane signaling pathway of which involves activation of phosphoinositide-specific phospholipase C, were compared in fetal (22 days gestation) and adult rat hepatocytes. Free cytosolic calcium changes varied depending on the agonist and type of stimulated cells. Angiotensin II and ATP elicited the maximal responses in both types of cells, whereas the maximal Ca2+ increase produced by vasopressin was twice as much in adult than in fetal hepatocytes. The opposite response was observed for bombesin- or gastrin-releasing peptide-stimulated cells. Triggering of fetal and adult hepatocytes with substances that maximally promote endoplasmic reticulum calcium release or phosphoinositide-specific phospholipase C activation revealed that at least for the actions mediated through the angiotensin II and P2 purinergic receptor, the agonist stimulation was near the maximal response capacity of the signaling pathway. Agreement was observed between the relative number of membrane receptors and the biological responses.
 ...
PMID:Differential calcium mobilization by vasopressin, angiotensin II, gastrin-releasing peptide, and adenosine triphosphate in adult and fetal hepatocytes. Relevance for the activation of calcium-dependent enzymes. 838 Mar 81

Hepatocytes were established in tissue culture in order to study the effects of pertussis toxin (PT) on epidermal growth factor (EGF)-mediated cellular responses under in vitro conditions. EGF caused a 3-fold increase of myo-inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) mass and a 50% increase of diacylglycerol mass within the first minute, with the change of diacylglycerol content being 100-fold greater than that of Ins-1,4,5-P3. Diacylglycerol, but not Ins-1,4,5-P3, continued to accumulate over several hours, indicating that EGF increased the hydrolysis of lipids other than phosphatidylinositol 4,5-bisphosphate (PIP2). EGF increased phosphoinositide-specific phospholipase C-gamma (PLC-gamma) tyrosine phosphorylation within 1 min, but no effect was observed with vasopressin, insulin, or glucagon after 5 min. EGF also caused a rapid, tyrosine kinase-dependent association of G(i) alpha with PLC-gamma, which was maximal within 10 min. In contrast to our previous data on fresh hepatocytes, PT had no effect on the EGF-induced tyrosine phosphorylation of PLC-gamma, although Ins-1,4,5-P3 and diacylglycerol production were inhibited. The role of G-proteins in EGF signaling was investigated further by microinjection of G alpha antibodies into single fura-2-loaded hepatocytes. Anti-G(i) alpha (common) antibodies prevented EGF-induced but not vasopressin-induced Ca2+ transients. These results strengthen previous observations that a PT-sensitive G-protein is involved in EGF-mediated phospholipid metabolism in hepatocytes and show that tyrosine phosphorylation of PLC-gamma is an insufficient signal for activation of PIP2 hydrolysis.
 ...
PMID:Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes. 842 49

Although several hormones that promote hepatocyte proliferation also activate phosphoinositide-specific phospholipase C (PI-PLC) and mobilize Ca2+, the role of PI-PLC in the growth-stimulating effect of these agents is not clear. We have investigated this issue further, by exposing freshly isolated adult rat hepatocytes to vasopressin, angiotensin II, norepinephrine (in the presence of the beta-adrenoceptor blocker timolol) or PGF2 alpha, and examined both acute responses and the subsequent DNA synthesis when the cells were grown in monolayer culture. All the agonists elevated the level of inositol 1,4,5-trisphosphate (InsP3) and enhanced the DNA synthesis, amplifying the response to epidermal growth factor (EGF), and this comitogenic effect could be exerted by a single exposure of the cells 24 h prior to the addition of EGF. The acute activation of PI-PLC, measured as the early rise (peak 15-60 s) in InsP3, was 8-10-fold with vasopressin or angiotensin II, 3-4-fold with norepinephrine, and approximately 2-fold with PGF2 alpha. For all the agonists, a rise in cytosolic free Ca2+ in 100% of the cells and a maximal increase in glycogen phosphorylase activity were evoked at concentrations that approximately doubled the level of InsP3. However, the growth-stimulatory effects of these agonists showed a different order of efficacy as compared to the activation of PI-PLC; in terms of the maximal stimulation of DNA synthesis, the effects were: norepinephrine approximately PGF2 alpha > angiotensin II > vasopressin. Also, norepinephrine, PGF2 alpha, and angiotensin II, but not vasopressin, further enhanced the DNA synthesis when their concentrations were increased above those yielding maximal elevation of InsP3. In experiments where vasopressin and angiotensin II were combined, their effects on the DNA synthesis were additive while the InsP3 responses were not. The results show that the extent of the initial activation of PI-PLC is not the determinant for the magnitude of the growth effects of Ca(2+)-mobilizing hormones in hepatocytes. This suggests either (a) that the proliferative response to these agents is determined by the activity of PI-PLC at a later time, or its integral over an extended part of the prereplicative period, rather than by the acute activation, or (b) that additional, PI-PLC-independent, mechanisms are required.
 ...
PMID:Growth-promoting effects of Ca(2+)-mobilizing agents in hepatocytes: lack of correlation between the acute activation of phosphoinositide-specific phospholipase C and the stimulation of DNA synthesis by angiotensin II, vasopressin, norepinephrine, and prostaglandin F2 alpha. 881 15

Several agents that act through G-protein-coupled receptors and also stimulate phosphoinositide-specific phospholipase C (PI-PLC), including angiotensin II, vasopressin, norepinephrine, and prostaglandin (PG) F2alpha, activated the ERK1 (p44mapk) and ERK2 (p42mapk) members of the mitogen-activated protein (MAP) kinase family in primary cultures of rat hepatocytes, measured as phosphorylation of myelin basic protein (MBP) by a partially purified enzyme, immunoblotting, and in-gel assays. All these agonists induced a peak activation (two to threefold increase in MBP-phosphorylation) at 3-5 min, followed by a brief decrease, and then a sustained elevation or a second increase of the MAP kinase activity that lasted for several hours. Although all the above agents also stimulated PI-PLC, implicating a Gq-dependent pathway, the elevations of the concentration of inositol (1,4,5)-trisphosphate did not correlate well with the MAP kinase activity. Furthermore, pretreatment of the cells with pertussis toxin markedly reduced the MAP kinase activation by angiotensin II, vasopressin, norepinephrine, or PGF2alpha. In addition, hepatocytes pretreated with pertussis toxin showed a diminished MAP kinase response to epidermal growth factor (EGF). The results indicate that agonists acting via G-protein-coupled receptors have the ability to induce sustained activation of MAP kinase in hepatocytes, and suggest that Gi-dependent mechanisms are required for full activation of the MAP kinase signal transduction pathway by G-protein-coupled receptors as well as the EGF receptor.
 ...
PMID:Activation of p42/p44 mitogen-activated protein kinase by angiotensin II, vasopressin, norepinephrine, and prostaglandin F2alpha in hepatocytes is sustained, and like the effect of epidermal growth factor, mediated through pertussis toxin-sensitive mechanisms. 957 80

Previous studies have shown that while vasopressin and angiotensin II are markedly more effective than norepinephrine and prostaglandin F2alpha in eliciting an acute elevation of inositol 1,4,5-trisphosphate (IP3), norepinephrine and prostaglandin F2alpha produce larger enhancement of DNA synthesis. This suggests that the initial activation of phosphoinositide-specific phospholipase C is not a common factor for the growth response to these agonists, but does not exclude a role of the integral of phospholipase C activity over a prolonged part of the prereplicative period, during which agonist-specific changes in responsiveness might occur. We show that vasopressin and angiotensin II also cause a prolonged elevation of cellular IP3 levels. which remain elevated for at least 60 min., while norepinephrine and prostaglandin F2alpha elevate IP3 levels slightly and transiently For vasopressin the dose-effect curves for IP3 accumulation and stimulation of DNA synthesis were closely parallel, while this was not the case for angiotensin II, norepinephrine, or prostaglandin F2alpha. After cultivation of the hepatocytes, hormone-stimulated IP3 accumulation rapidly declined, particularly in response to norepinephrine and prostaglandin F2alpha. When the IP3 response to norepinephrine and prostaglandin F2alpha was completely down-regulated, these agonists still enhanced the DNA synthesis. These results suggest that other mechanisms in addition to IP3 accumulation and Ca2+ release are likely to be involved in the growth stimulatory effects of the Ca2+-mobilizing agonists studied here, in particular for angiotensin II, norepinephrine, and prostaglandin F2alpha.
 ...
PMID:The relationship between activation of phosphoinositide-specific phospholipase C and growth stimulation by Ca2+-mobilizing hormones in hepatocytes. 1036 80

It was previously found that pertussis toxin (PTX) pretreatment inhibits the activation of extracellular signal-regulated kinases ERK1 (p44(mapk)) and ERK2 (p42(mapk)) in hepatocytes in response to either agonists that bind to heptahelical receptors or epidermal growth factor (EGF), suggesting a role of G(i) proteins in stimulatory mechanisms for ERK1/2. The present work shows that ERK1/2 is activated in a PTX-sensitive way not only by vasopressin, angiotensin II, prostaglandin (PG) F(2alpha), alpha(1)-adrenergic stimulation, and EGF but also by agents whose actions bypass receptors and stimulate protein kinase C (PKC) and/or elevate intracellular Ca(2+), such as 12-O-tetradecanoyl phorbol-13-acetate (TPA), exogenous phosphatidylcholine-specific phospholipase C (PC-PLC, from Bacillus cereus), thapsigargin, and the Ca(2+) ionophore A23187. Under the same conditions, PTX did not affect agonist stimulation of phosphoinositide-specific phospholipase C (PI-PLC) (IP(3) generation), and did not reduce the activation by these agents of phospholipase D (PLD). The results suggest that in hepatocytes a PTX-sensitive mechanism, presumably involving G(i) proteins, exerts a stimulatory effect on ERK at a level distal to receptor coupling, acting either as an integral part of the signaling pathway(s) or by a permissive, synergistic regulation.
 ...
PMID:Effects of pertussis toxin on extracellular signal-regulated kinase activation in hepatocytes by hormones and receptor-independent agents: evidence suggesting a stimulatory role of G(i) proteins at a level distal to receptor coupling. 1082 31

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.
 ...
PMID:Fuel and hormone regulation of phospholipase C beta 1 and delta 1 overexpressed in RINm5F pancreatic beta cells. 1137 26


<< Previous 1 2