Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to determine the roles of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the regulation of adrenocorticotropin (ACTH) secretion in perfused ovine anterior pituitary (AP) cells and their ability to cause protein phosphorylation and dephosphorylation in these cells. Freshly dispersed ovine AP cells were maintained in a miniperifusion chamber and ACTH secretion was monitored every 20 s. When cells were perfused with CRF (1 nM, 5 min) or AVP (1 nM, 5 min), ACTH release was increased 20-fold and 12-fold, respectively. When an ovine AP cell membrane fraction was incubated with either CRF or AVP, CRF stimulated the phosphorylation of at least 11 proteins and the dephosphorylation of at least 5 phosphoproteins, whereas AVP caused the phosphorylation of at least 15 proteins and the dephosphorylation of 5 proteins. A comparison of the proteins phosphorylated by CRF or AVP with those phosphorylated by cAMP or protein kinase C activators suggested that the hormone-stimulated phosphorylation may also involve unidentified protein kinases. Additionally, at least eight proteins appeared to be phosphorylated by both CRF and AVP. Furthermore, in the case of four particular proteins both CRF and AVP stimulated phosphorylation at low concentrations of Ca2+ (0.1-1 microM), but at high concentrations of Ca2+ (10-100 microM) CRF or AVP triggered dephosphorylation of these proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of the mechanisms of action of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the ovine anterior pituitary: evidence that CRF and AVP stimulate protein phosphorylation and dephosphorylation. 789 15

Previous studies have demonstrated that prostaglandin E2 (PGE2) inhibits arginine vasopressin-(AVP)dependent adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in microdissected rat outer medullary collecting tubules (OMCD), by a mechanism unrelated to the inhibition of cAMP synthesis. The potential role of the activation of protein kinase C (PKC) to explain the negative regulation elicited by PGE2 was investigated in this study. Single OMCD samples were pre-incubated (10 min, 30 degrees C) in the presence or absence of either activators of PKC, phorbol 12-myristate 13-acetate (PMA), 1-oleoyl-2-acetyl-glycerol (OAG), dioctanoylglycerol (DOG) or an inhibitor of PKC, staurosporine (SSP). These compounds were present also with the agonists tested during the incubation period (4 min, 35 degrees C). In contrast to PGE2, activators of PKC did not decrease AVP-dependent cAMP accumulation (mean +/- SEM): 1 nM AVP = 47.1 +/- 6.8 fmol.mm-1 x 4 min-1; AVP+0.3 microM PGE2 = 20.1 +/- 2.7, P < 0.01 versus AVP; AVP + 10 nM PMA = 42.0 +/- 4.7, NS versus AVP; AVP + 50 micrograms/ml OAG = 44.1 +/- 4.8. NS versus AVP, N = 5 experiments. However, 10 nM PMA prevented PGE2-induced inhibition: AVP + PGE2 = 44.2 +/- 3.5% of the response to AVP and 90.3 +/- 3.2% without and with PMA respectively, N = 16. Similar results were obtained with either 50 micrograms/ml OAG or 25 micrograms/ml DOG (AVP + PGE2 + OAG = 92.9 +/- 6.6% of the response to AVP, N = 8; AVP + PGE2 + DOG = 94.1 +/- 5.3%, N = 7).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The activation of protein kinase C prevents PGE2-induced inhibition of AVP-dependent cAMP accumulation in the rat outer medullary collecting tubule. 790 84

Arginine vasopressin has been shown to activate the Na+/H+ exchanger in hepatocytes by calcium/calmodulin-dependent processes. Whether this activation also involves protein kinase C and is associated with changes in the intracellular pH setpoint was investigated in this study. Changes in pHi and intracellular Ca++ concentration were measured with the fluorescent probes BCECF and quin-2, respectively. Intracellular pH recovery rate was calculated from time-dependent changes in intracellular pH in hepatocytes acid-loaded with sodium propionate. Arginine vasopressin, phorbol myristate acetate and thapsigargin stimulated intracellular pH recovery but did not increase basal intracellular pH. Arginine vasopressin and thapsigargin, but not phorbol myristol acetate, increased intracellular Ca++ concentration. The protein kinase C inhibitors staurosporine and calphostin C inhibited arginine vasopressin- and phorbol myristol acetate-induced, but not thapsigargin-induced, intracellular pH recovery. Neither staurosporine nor calphostin C affected arginine vasopressin- and thapsigargin-induced increases in intracellular Ca++ concentration, and no inhibitor affected basal intracellular pH recovery. Arginine vasopressin, phorbol myristol acetate and thapsigargin increased intracellular pH dependency of intracellular pH recovery without affecting intracellular pH setpoint. These results indicate that the activation of the Na+/H+ exchanger by arginine vasopressin is mediated both by Ca++/calmodulin and protein kinase C and may be due to enhanced interaction of H+ with the internal modifier site of the exchanger.
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PMID:Mechanism of activation of the Na+/H+ exchanger by arginine vasopressin in hepatocytes. 792 66

Incubation of cultured rat aortic smooth muscle cells (ASMCs) in a medium containing high glucose concentrations (25 mM) did not affect the basal cytosolic free calcium ([Ca2+]i) but led to significant reductions in peak [Ca2+]i response evoked by arginine vasopressin, angiotensin II, and endothelin-1 (ET-1). This was observed in both the presence and absence of extracellular Ca2+. Maintenance of rat ASMCs in a medium containing mannose (an osmotic control for high glucose) did not affect either the basal or peptide agonist-evoked increase in [Ca2+]i. However, pretreatment with either the nonselective protein kinase C (PKC) inhibitor staurosporine or the selective PKC inhibitor 2,6-diamino-N-([1-(1-oxotridecyl)-2 piperidinyl] methyl) hexanamide reversed the attenuating effect of high glucose on peak [Ca2+]i response evoked by ET-1. Also, short-term incubation of ASMCs with the active phorbol ester, phorbol 12-myristate 13-acetate, led to a reduction in peak [Ca2+]i response to all three agonists, whereas the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate, which does not activate PKC, had no such effect. Although high-glucose treatment of rat ASMCs led to significant reductions in the maximal number of binding sites to the extent of 39% of [125I]ET-1 specific binding, no significant differences in the affinity (Kd approximately 110 pM) characteristics were evident between control and high-glucose treatment groups. It is proposed that incubation of rat ASMCs with high glucose enhances the de novo synthesis of diacylglycerol and activates membrane-bound PKC and that this, in turn, impairs agonist-mediated intracellular Ca2+ mobilization.
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PMID:High glucose attenuates peptide agonist-evoked increases in cytosolic free [Ca2+] in rat aortic smooth muscle cells. 803 97

The immature kidney is characterized by resistance to arginine vasopressin (AVP). In the immature cortical collecting duct (iCCD), AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation is decreased, but the mechanisms involved are not known. We examined cAMP production in isolated CCD from immature and mature rabbits. Cellular cAMP levels were measured by radioimmunoassay under basal conditions and after stimulation with hormone. Basal cAMP production in the iCCD was not different from that in the mature CCD (mCCD). In contrast, AVP- and forskolin-stimulated cAMP generation were severely decreased in the iCCD. Inhibition of endogenous prostaglandin production by indomethacin increased AVP-stimulated cAMP generation in the iCCD to levels that were not different from the mCCD. Inhibition of protein kinase C (PKC) by staurosporine and inhibition of Gi by pertussis toxin elicited a mature cAMP response in the iCCD. These data suggest that the defect in AVP-stimulated cAMP production in the iCCD is mediated by prostaglandins via 1) activation of Gi and 2) direct inhibition of the adenylyl cyclase catalytic subunit. In addition, PKC appears to play a significant role.
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PMID:Prostaglandins mediate the defect in AVP-stimulated cAMP generation in immature collecting duct. 804 63

Peptide hormones control salt reabsorption in cortical thick ascending limb (cTAL) cells of the loop of Henle. These agonists act, in part, through alterations on intracellular Ca2+ ([Ca2+]i). Primary cell cultures were prepared from porcine kidneys using a double antibody technique (goat antihuman Tamm-Horsfall and rabbit antigoat IgG antibodies). [Ca2+]i was determined in single cells with fluorescent techniques using fura-2. Parathyroid hormone (PTH) and arginine vasopressin (AVP) transiently increased [Ca2+]i in a dose-dependent manner. [Ca2+]i maximally increased from 85 +/- 5 nmol/l to 608 +/- 99 nmol/l with PTH, 10(-6) M, and to 766 +/- 162 nmol/l with AVP, 10(-7) M. The increment in [Ca2+]i by both hormones was by intracellular Ca2+ release and entry through plasma membrane Ca2+ channels. 8-Bromo-adenosine-3',5'-cyclic monophosphate (8-BrcAMP), 10(-4) M, increased [Ca2+]i (basal 83 +/- 3 to 427 +/- 121 nmol/l) but only from internal sources as nifedipine (10 mumol), ([Ca2+]i changes: 86 +/- 4 to 390 +/- 29 nmol/l) and removal of bath Ca/+o, ([Ca2+]i changes: 84 +/- 6 to 517 +/- 142 nmol/l), were without effect on agonist-induced [Ca2+]i. Thapsigargin, 1.5 mumol, completely abolished the AVP- and cyclic adenosine monophosphate-(cAMP)-induced Ca2+ transients, and partially inhibited PTH-mediated Ca2+ transients by about 50%. Pretreatment with 8-BrcAMP inhibited the PTH and AVP responses likely through depletion of cAMP-sensitive Ca2+ stores. Activation of protein kinase C (PKC) with phorbol esters inhibited PTH and AVP responses and 8-BrcAMP-induced [Ca2+]i transients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormone-mediated Ca2+ transients in isolated renal cortical thick ascending limb cells. 805 57

The present study was designed to examine whether heparin inhibits basal or stimulated endothelin-1 production by arginine vasopressin (AVP) and platelet-derived growth factor (PDGF) in cultured rat mesangial cells. In addition, the reversibility of the heparin effect on mesangial cell endothelin-1 production was examined. AVP and PDGF stimulated endothelin-1 secretion in a concentration-dependent manner in these cells. Heparin (10 to 100 U/ml) exhibited concentration-related inhibition of AVP- and PDGF-stimulated endothelin-1 secretion. Heparin also had weak but significant inhibitory effects on basal endothelin-1 secretion in these cells. The protein kinase (PKC)-activating phorbor ester, phorbor myristate acetate (PMA), stimulated endothelin-1 secretion and heparin inhibited PMA-stimulated endothelin-1 secretion. In addition, the inhibitory effect of heparin was completely abolished in PKC-depleted mesangial cells. Mesangial cells which were exposed to a high concentration (100 U/ml) of heparin for 24 hours were capable of producing endothelin-1 after a short lag period of removal of heparin from the culture medium. These mesangial cells also showed recovery of responses to AVP and PDGF by secreting a significantly greater amount of endothelin-1 than the non-stimulated level. These results indicate that heparin potently inhibits mesangial cell endothelin-1 production, especially when stimulated by AVP or PDGF. This inhibitory effect of heparin is probably PKC dependent, and reversible.
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PMID:Heparin inhibits endothelin-1 production in cultured rat mesangial cells. 812 2

Exposure of cultured, spontaneously beating rat cardiomyocytes to arginine vasopressin (AVP) led to marked increases in the release of prostacyclin (PGI2) and atrial natriuretic peptide (ANP). These responses were accompanied by a rapid, transient rise of cytosolic free Ca2+ concentration ([Ca2+]i) and of membranous protein kinase C (PKC) activity. Ca2+ influx and PKC activity appeared to play important but distinct roles in AVP-induced cellular responses, insofar as only AVP-induced ANP secretion was abolished by the Ca2+ channel antagonist nifedipine, whereas both AVP-induced PGI2 production and ANP release were abolished by the PKC inhibitors staurosporine and CGP-41251. The AVP-induced increase in [Ca2+]i could also be mimicked with the vasopressin (V1-subtype) agonist Octapressin, but not with the V2-agonist 1-desamino-8-D-arginine vasopressin, and was fully abolished by the V1-antagonist [d(CH2)5Tyr(Me)]AVP, but not by d(CH2)5-D-Leu-VAVP (V1-/V2-antagonist). These results indicate that V1-vasopressinergic receptors mediate AVP-induced PGI2 production and ANP secretion in rat cardiomyocytes and that, whereas both Ca2+ influx and PKC activation are required for AVP-induced ANP secretion, AVP-induced PGI2 formation is mainly regulated by PKC.
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PMID:[Ca2+]i and protein kinase C in vasopressin-induced prostacyclin and ANP release in rat cardiomyocytes. 814 61

In rat inner medullary collecting tubule (RIMCT) cells increasing cytosolic Ca2+ with a calcium ionophore inhibits arginine vasopressin (AVP)-stimulated adenylyl cyclase (AC). Inhibition by Ca2+ is not observed in pertussis toxin (PT)-treated cells, indicating a role for the inhibitory G protein, Gi. The mechanism of activation of Gi remains to be determined. We examined the hypothesis that inhibition of AVP-stimulated AC by increased cytosolic Ca2+ is due to activation of protein kinase C (PKC). Preincubation of RIMCT cells with ionophore results in inhibition of AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation. To assess whether stimulation of phospholipase C (PLC) and therefore activation of PKC occurs with ionophore and AVP, inositol trisphosphate (IP3) production was measured. Incubation of RIMCT cells with either 10(-7) M AVP or ionophore results in IP3 production that is no different from basal. However, simultaneous exposure to 100 nM AVP with ionophore results in marked enhancement of IP3 production clearly reflecting stimulation of PLC in this setting. Stimulation of PLC is not observed in PT-treated cells. Likewise, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of PKC, mimics the effect of PT to prevent inhibition of AVP-stimulated AC by ionophore, but N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide (H-8), an inhibitor of protein kinase A (PKA), does not. As is the case when PKC is stimulated directly with a phorbol ester, exposure to ionomycin inhibits the response to AVP but does not alter the response to isoproterenol. These studies demonstrate that increased cytosolic Ca2+ does not, as previously postulated, inhibit AC by a direct effect on Gi. Rather, when cytosolic Ca2+ is increased, AVP stimulates PLC; the ensuring activation of PKC inhibits cAMP formation.
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PMID:Increased cytosolic Ca2+ inhibits AVP-stimulated adenylyl cyclase activity in rat IMCT cells by activation of PKC. 816 Jul 98

Changes in cytosolic free calcium concentration ([Ca2+]i) induced by angiotensin II (ANG II), arginine vasopressin (AVP), angiotensin III (ANG III), norepinephrine (NE), or thapsigargin were investigated after inhibition of the Na(+)-Ca2+ exchange in vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats by use of the fluorescent dye technique. The ANG II-induced peak [Ca2+]i increase was significantly enhanced after inhibition of Na(+)-Ca2+ exchange by NiCl2 or 1,3-dimethyl-2-thiourea (DMTU): control, 99 +/- 9 (SE) nM (n = 64); NiCl2, 181 +/- 23 nM (n = 23; P < 0.01); DMTU, 182 +/- 35 nM (n = 10; P < 0.05). In the absence of external calcium, the inhibition of the Na(+)-Ca2+ exchange by NiCl2 also enhanced the ANG II-induced [Ca2+]i increase. Inhibition of Na(+)-Ca2+ exchange by removal of external sodium, which was replaced by choline, augmented the ANG II-induced [Ca2+]i increase to 174 +/- 26 nM (n = 11; P < 0.05 compared with control). The inhibition of the protein kinase C activity by isoquinoline-sulfonyl-O-2-methylpiperazine blocked the enhancing effect of NiCl2 on ANG II-induced [Ca2+]i increase. The inhibition of the Na(+)-Ca2+ exchange did not enhance the increase in [Ca2+]i induced by ANG III, NE, or thapsigargin. The AVP-induced changes in [Ca2+]i were not significantly different in the presence or absence of NiCl2. It is concluded that the recovery of resting [Ca2+]i after stimulation by ANG II is mediated by calcium efflux via the Na(+)-Ca2+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of Na(+)-Ca2+ exchange in agonist-induced changes in cytosolic Ca2+ in vascular smooth muscle cells. 816 43


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