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)

An enriched rat Leydig cell preparation was preincubated with [14C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 microM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol and phosphatidylinositol 4-monophosphate + phosphatidylinositol 4,5-bisphosphate. Preincubation with dibutyryl cyclic AMP had no effect on the AVP-induced phospholipid turnover. Leydig cells were preincubated with myo-[2-3]inositol for 22 h and then with 10 mM LiCl for 10 min. Exposure to AVP (1 microM) induced a rise in labelled inositol phosphates. The response was inhibited when the cells were preincubated with the phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (0.16 microM) for 10 min. These results provide evidence for an AVP-induced phospholipase C stimulation in rat Leydig cells and suggest a protein kinase C-dependent feedback inhibition of the stimulation. Other agonists that might have a regulatory function in the testis were tested for possible effects on phosphoinositide metabolism. Of prostaglandin E2 (10 microns,) angiotensin II (0.1 microM), and bradykinin (0.9 microM), only the latter induced a significant increase in the labelled inositol phosphates. This suggests that Leydig cells possess a bradykinin receptor which can activate phospholipase C.
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PMID:Arginine vasopressin stimulates phosphoinositide turnover in an enriched rat Leydig cell preparation. 253 41

Stimulation of vasopressin (V1) receptors of rat aortic smooth muscle cells (A-10, ATCC CRL 1476) results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) with the mobilization of intracellular calcium. When A-10 cells are exposed to arginine vasopressin (AVP), there is an increase in the level of c-fos oncoprotein. The extent of induction of c-fos oncoprotein depends on both the time of exposure of the cells to AVP, reaching a maximum at 60 min after which there is a slow decline, and the concentration of AVP used, with an approximate EC50 of 1 nM which corresponds well with the Kd of vasopressin binding to these receptors. This vasopressin-mediated increase in c-fos protein level is inhibited by a V1/V2 antagonist (SKF 101498) suggesting that this is a receptor-mediated event. In addition dDAVP, a V2 selective agonist, is much less effective than AVP in inducing c-fos protein suggesting that AVP mediates its effect via V1 receptors. Desensitization of vasopressin receptors by prolonged exposure to AVP resulted in no additional induction of c-fos protein level in response to second challenge of AVP. In addition to AVP, phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC), also stimulates the accumulation of c-fos protein although to a lesser extent than AVP. The above data suggest that c-fos protein levels in smooth muscle cells are regulated by AVP and the hormonal effect may be mediated through PI turnover and DAG, IP3 and Ca2+ signals.
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PMID:Induction of c-fos protein by activation of vasopressin receptors in smooth muscle cells. 253 65

This study explored an effector mechanism associated with the arginine vasopressin (AVP) recognition site in the hippocampus, namely, potentiation of norepinephrine (NE)-induced cAMP accumulation in the surviving hippocampal slice. The biochemical mechanisms that underlie the AVP potentiation were investigated as follows: First, the actions of AVP upon NE-induced accumulation of cAMP in hippocampal slices from rat brain were specific to AVP and not shared by other closely related peptides, namely, oxytocin and AVP4-9. Second, the AVP-induced neuromodulation involved beta-adrenergic receptors, with AVP having no effect on cAMP levels in the absence of NE. Third, the potentiation by AVP was biphasic, with lower AVP concentrations potentiating NE-induced cAMP accumulation, while higher concentrations did not potentiate. Fourth, an antagonist of V1-type AVP receptors blocked AVP potentiation. Fifth, AVP potentiation was dependent upon extracellular calcium concentrations. Sixth, AVP potentiation was blocked by 50 microM trifluoperazine, which is consistent with a calcium-calmodulin involvement but which might also implicate protein kinase C. These alternatives and the nature of the calcium involvement are discussed. AVP actions thus appear to involve interactions between several second-messenger systems and suggest a biochemical mechanism by which AVP exerts its centrally mediated behavioral effects.
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PMID:Vasopressin neuromodulation in the hippocampus. 256 30

In cortical collecting ducts (CCD), arginine vasopressin (AVP) has been proposed to autoinhibit its own hydrosmotic effect through stimulation of prostaglandin (PG) synthesis or binding to a receptor coupled to phosphatidylinositol (PI) hydrolysis, the so-called V1-receptor, with resultant elevation of intracellular Ca2+ concentration [( Ca2+]i) and activation of protein kinase C (PKC). Using isolated perfused rabbit CCD, we examined whether blocking the negative feedback by a PKC inhibitor, staurosporine (SSP), or a cyclooxygenase inhibitor, indomethacin (IND), enhances AVP-induced increase in hydraulic conductivity (Lp). The Lp induced by a pharmacological concentration (23 nM) of AVP was lower than that induced by 230 pM AVP. This blunted Lp response to 23 nM AVP was significantly restored by SSP or IND pretreatment. In contrast, both SSP and IND did not affect the Lp induced by 23 pM or 230 pM AVP. Fluorescence microscopy of isolated perfused CCD using fura-2 showed a spike-like increase in [Ca2+]i only by 23 nM but not by 23 or 230 pM AVP. We conclude that 1) AVP can increase [Ca2+]i, activate PKC, and stimulate PG synthesis in CCD with resultant autoregulation of its own hydrosmotic effect and 2) importantly, however, this negative feedback occurs only with pharmacologically high concentrations of AVP. Therefore it is unlikely that circulating AVP, via binding to receptors on CCD, autoregulates water transport through activating PG synthesis and/or PI breakdown.
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PMID:Dose-dependent heterogenous actions of vasopressin in rabbit cortical collecting ducts. 270 33

Vascular smooth muscle cell (VSMC) contraction is the result of several interacting mechanisms. In this study such interactions in rat aortic VSMC in culture were examined with a focus on the role of protein kinase C-mediated mechanisms. The change in shape of VSMC was used as a functional parameter representative of contraction. The protein kinase C agonist, phorbol myristate acetate (PMA), and arginine vasopressin (AVP) induced a dose-dependent, progressive change in VSMC shape. The effects of PMA differed from AVP in the delay time necessary to reach the plateau of the response and in the absence with PMA of a transient rise in cytosolic free Ca2+ [( Ca2+]i). The effect of PMA was potentiated by the Ca2+ ionophore, ionomycin, and involved a verapamil-inhibitable transmembrane Ca2+ transport system. Protein kinase C inhibition by either isoquinolin-sulfonyl-O-2-methylpiperazine or protein kinase C desensitization significantly reduced the cell shape change induced by either PMA or AVP. In the case of AVP, this inhibitory effect occurred without affecting the [Ca2+]i transient. Therefore, the [Ca2+]i transient appears to be independent of acute protein kinase C regulation, since it is apparently not affected by the absence of protein kinase C activity. Protein kinase C activation by PMA produced intracellular alkalinization that is blocked by the sodium transport antagonist, amiloride. Amiloride also blocked the cell shape change induced by PMA or AVP. The intracellular alkalinization, however, was not necessary for the cell shape change to occur. Specifically, with the use of VSMC preincubated with fetal calf serum, PMA did not induce cellular pH changes but still produced cell shape changes.
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PMID:Phorbol esters and arginine vasopressin in vascular smooth muscle cell activation. 271 20

Prior exposure of immature rat testis to arginine vasopressin caused the testis refractory at 24 h in terms of ornithine decarboxylase activity. Arginine vasopressin caused desensitization both in Leydig cells and seminiferous tubules. Arginine vasopressin induced desensitization was found to be both time and dose-dependent. Arginine vasopressin desensitized testis was refractory to luteinizing hormone, follicle stimulating hormone, norepinephrine, dibutyryl cAMP, phorbol-myristate acetate and cholera toxin at 24 h. Arginine vasopressin desensitized testis showed recovery of response to norepinephrine at 48 h after the first injection. On the contrary arginine vasopressin could stimulate ornithine decarboxylase in luteinizing hormone desensitized testis. These results indicate that in arginine vasopressin desensitized testis the block is at post cAMP step which is common to both cAMP dependent and protein kinase C-diacylglycerol system in stimulating testicular ornithine decarboxylase.
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PMID:Desensitization of immature rat testicular ornithine decarboxylase to arginine vasopressin. 282 80

The tumor promoter, tetradecanoylphorbolacetate (TPA), causes a significant increase in both insulin secretion and the incorporation of 32Pi into phosphatidylcholine (PC) in RIN insulinoma cells. The peptide hormone, arginine vasopressin (AVP), also stimulates these functions, although to a lesser degree. When added together, the effects on secretion and PC metabolism are synergistic. At the same time, TPA inhibits the AVP-stimulated rise in phosphoinositide (PI) metabolism. Neither phloretin nor tamoxifen, reported to be inhibitors of protein kinase C activity, are able to block the effects of TPA on secretion, although both influence PC metabolism.
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PMID:Synergism between vasopressin and phorbol esters in stimulation of insulin secretion and phosphatidylcholine metabolism in RIN insulinoma cells. 283 2

Epidermal growth factor (EGF) is a 53-amino acid polypeptide which is a potent mitogen for cultured cells. The kidney has recently been shown to be a major site of synthesis for the EGF precursor. EGF infusions in sheep result in a diuresis and natriuresis despite a fall in GFR, suggesting a direct tubular effect. Using in vitro microperfusion of rabbit cortical collecting tubules (CCTs) at 37 degrees C, we examined the effect of EGF on the transepithelial voltage (Vt) and arginine vasopressin (AVP)-stimulated hydraulic conductivity (Lp). Pretreatment with peritubular EGF at concentrations from 10(-8) to 10(-12) M resulted in a 50% inhibition of both AVP- and 8-chlorophenythio-cyclic AMP-stimulated peak Lp. This effect was reversed by the protein kinase C inhibitor, staurosporine, but unaffected by indomethacin. CCTs with an initially negative Vt, depolarized after exposure to bath EGF. 10(-8) M EGF applied from the lumen had no effect on either Lp or Vt. Specific binding of 20 nM 125I-EGF to microdissected CCTs was also demonstrated. These results suggest that EGF can modulate both salt and water transport in the CCT via a receptor linked to protein kinase C activation.
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PMID:Epidermal growth factor inhibits the hydroosmotic effect of vasopressin in the isolated perfused rabbit cortical collecting tubule. 284 52

A growing body of evidence indicates that aminoglycoside antibiotics interact with phosphoinositides and this has led to the hypothesis that these drugs perturb the phosphatidylinositol (PI) cascade. To test this hypothesis we examined the effect of gentamicin on agonist stimulation of the PI cascade in primary culture of rabbit proximal tubular cells (RPTC) and in rat renal cortex. Parathyroid (PTH) (10(-6) M) stimulated a significant increase in total inositol phosphates, inositol monophosphate and inositol trisphosphate, but not inositol bisphosphate in RPTC with the peak effect at 2 min. This effect was completely inhibited in RPTC exposed to 10(-3) M gentamicin for 48 and 24 hr. In other experiments we demonstrated that angiotensin II, phenylephrine, bradykinin and arginine vasopressin (all at 10(-6) M) stimulated inositol trisphosphate generation in control RPTC but not in cells exposed to 10(-3) M gentamicin for 24 h. In contrast gentamicin did not block PTH-stimulation of cyclic AMP generation, which indicates that gentamicin did not prevent PTH from interacting with its plasma membrane receptor. PTH also stimulated redistribution of protein kinase C from the cytosolic to the membrane fraction of RPTC. This effect was completely abolished in RPTC exposed to 10(-3) M gentamicin for 2 days. PTH given i.p. to rats stimulated the redistribution of protein kinase C from the cytosolic to the membrane fraction of renal cortex. This effect was completely inhibited in rats injected with gentamicin, 100 mg/kg per day for 2 days. The
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PMID:Gentamicin inhibits agonist stimulation of the phosphatidylinositol cascade in primary cultures of rabbit proximal tubular cells and in rat renal cortex. 284 80

It was the aim of the present study to get insight into some of the intracellular mechanisms by which the vasoconstrictor hormones angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE) inhibit renin release from renal juxtaglomerular cells. To this end a primary cell culture from rat renal cortex was established that consisted of 50% juxtaglomerular cells. The cultured juxtaglomerular cells contained prominent renin granules closely resembling those in the intact kidney and responded to a number of stimuli of renin release. By using these cultures, we found that ANG II (10(-7) M), AVP (10(-6) M), and NE (10(-5) M) inhibited renin release and increased the calcium permeability of the plasma membrane of the cultured cells. Both the effects on renin release and on calcium permeability could be diminished or even be abolished by the calcium channel blocker verapamil (Vp) (10(-5) M). ANG II, AVP, and NE led to an increased formation of diacylglycerol (DAG), a well-known stimulator of protein kinase C (PKC). Moreover, a direct stimulation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) (10(-8)-10(-6) M) also inhibited renin release and increased the calcium permeability of the cell membrane. Similar to ANG II, AVP, and NE, the effects of TPA on calcium permeability and renin release could be diminished by Vp. In conclusion, these results point toward a common mechanism by which vasoconstrictors inhibit renin release from renal juxtaglomerular cells: ANG II, AVP, and NE activate a phospholipase C, which generates DAG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of protein kinase C in inhibition of renin release caused by vasoconstrictors. 300 66


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