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

The preincubation of vascular smooth muscle cells (VSMC) with a non-peptide arginine vasopressin (AVP) antagonist (OPC-21268) (0.5 mM) for 10 min completely inhibited the 1 microM AVP-induced activation of mitogen-activated protein (MAP) kinase but did not affect the angiotensin II-, protein kinase C activator- or ionomycin-stimulated MAP kinase. Similar results were obtained with the simultaneous administration of AVP and OPC-21268. This inhibitory effect of OPC-21268 completely disappeared after washing the cells pretreated with OPC-21268. In contrast, the preincubation of VSMC with a peptide AVP antagonist, d(CH2)5Tyr(Me)AVP (1 microM), for 10 min completely blocked the 1 microM AVP-activated MAP kinase but the simultaneous administration of d(CH2)5Tyr(Me)AVP with AVP could inhibit that only by 40%. However, the washing procedure did not affect the inhibitory effect of d(CH2)5Tyr(Me)AVP. These results indicate that OPC-21268 is a specific AVP antagonist to inhibit the AVP-induced activation of MAP kinase. The antagonistic effect of OPC-21268 is also suggested to be relatively weak but prompt as compared to that of a peptide AVP antagonist d(CH2)5Tyr(Me)AVP.
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PMID:Distinct inhibition by non-peptide and peptide arginine vasopressin antagonists of vasopressin-induced activation of mitogen-activated protein kinase in cultured rat vascular smooth muscle cells. 817 97

The effect of the antidiarrheal drug loperamide, a mu-opiate agonist, on ACTH secretion and biosynthesis, cAMP generation and phosphoinositide turnover was studied in rat anterior pituitary cell cultures. The cAMP-dependent protein kinase A pathway was stimulated with both corticotropin-releasing hormone (CRH; 2-5 nM) and the membrane-permeable Bu(2)cAMP (0.5-2.5 mM). The protein kinase C pathway was stimulated with 1 microM arginine vasopressin (AVP) and 1-10 nM phorbol 12-myristate 13-acetate (PMA). After 3.5 h, loperamide (10 microM) had no effect on basal ACTH levels but significantly suppressed CRH-induced ACTH release, in a dose-dependent manner, to 60 +/- 4% of control (100%) (p < 0.0001). After 24 h, basal proopiomelanocortin mRNA was significantly decreased to 50% of control by loperamide (p < 0.05). The suppressive effect of loperamide on CRH-induced ACTH secretion was not reversible by naloxone (0.1-1,000 microM). Morphine (0.01-10 microM) had no effect on basal and CRH-induced ACTH secretion. Loperamide did not influence basal and CRH-induced adenylate cyclase activity in anterior pituitary cell membrane preparations, but it significantly blunted Bu(2)cAMP-induced ACTH secretion in cell culture from 100 +/- 4 to 77 +/- 4% (p < 0.05). In Ca(2+)-depleted medium (Ca2+ < 0.1 mM), loperamide had no suppressive effect on CRH-induced ACTH secretion. AVP-induced ACTH secretion was significantly suppressed by loperamide from 100 +/- 5 to 74 +/- 3% (p < 0.0001), while basal and AVP-induced inositol 1-phosphate generation and PMA-induced ACTH secretion were not affected by loperamide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Loperamide inhibits corticotrophic cell function by a naloxone-insensitive mechanism in the rat in vitro. 823 60

Experiments examined the effects of elevation of intracellular calcium concentration ([Ca2+]i) or activation of protein kinase C (PKC) on Na+ and water transport in the rat cortical collecting duct (CCD). We measured the lumen-to-bath 22Na+ flux (J1-->b), transepithelial voltage (VT), and water permeability (Pf) in CCD from deoxycorticosterone (DOC)-treated rats. Ionomycin (0.5 and 1 microM) and thapsigargin (1 and 2 microM) were used to increase [Ca2+]i. Phorbol 12-myristate 13-acetate (PMA; 0.3 and 1 microM) and oleoyl-acetyl-glycerol (OAG; 100 microM) were used as activators of PKC. [Ca2+]i was measured in isolated perfused tubules using the fluorescent dye fura 2. When added to the bathing solution, 220 pM arginine vasopressin (AVP) failed to affect [Ca2+]i, whereas 1 microM ionomycin increased [Ca2+]i by 103 +/- 15% and 2 microM thapsigargin increased [Ca2+]i by 24 +/- 4%. In flux studies, neither ionomycin nor thapsigargin affected J1-->b or Pf, although ionomycin caused marked morphological changes. Ionomycin also failed to alter either parameter in tubules from non-DOC-treated rats. Neither 100 microM OAG nor 1 microM PMA affected J1-->b or Pf. OAG at 50 microM had no effect on VT or transepithelial resistance, indicating no inhibition of conductive Na+ transport. We conclude that increased [Ca2+]i and PKC activation do not affect J1--b or Pf in the rat CCD. These findings may account for the sustained increase in J1--b produced in the rat CCD by AVP.
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PMID:Intracellular Ca2+ and PKC activation do not inhibit Na+ and water transport in rat CCD. 823 86

The present study was undertaken to examine the effects of diminished extracellular sodium concentration on the vascular action of arginine vasopressin (AVP) in cultured rat vascular smooth muscle cells (VSMC). The preincubation of cells with the 110 mM extracellular Na+ ([Na+]e) solution supplemented with 30 mM choline chloride for 60 minutes enhanced the effect of AVP- (1 x 10(-8) M) induced VSMC contraction. The treatment of 110 mM [Na+]e solution also enhanced the cellular contractile response to the protein kinase C (PKC) activators, phorbol 12-myristate 13-acetate and 1-oleoyl-2-acetyl-glycerol. Furthermore, preincubation with the 110 mM [Na+]e solution also potentiated the effect of 1 x 10(-8) M AVP, but not 1 x 10(-6) M, to increase the cytosolic-free Ca2+ ([Ca2+]i) concentration. The 110 mM [Na+]e media decreased the basal intracellular Na+ concentration and increased intracellular 45Ca2+ accumulation, basal [Ca2+]i and AVP-produced 45Ca2+ efflux. These effects of 110 mM [Na+]e solution to enhance the vascular action of AVP were abolished by using Ca(2+)-free 110 mM [Na+]e solution during the preincubation period. The preincubation with the 110 mM [Na+]e solution did not change either the Kd and Bmax of AVP V1 receptor of VSMC or the AVP-induced production of inositol 1,4,5-trisphosphate. The present in vitro results therefore indicate that the diminished extracellular fluid sodium concentration within a range observed in clinical hyponatremic states enhances the vascular action of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancement of vascular action of arginine vasopressin by diminished extracellular sodium concentration. 825 53

Studies were performed to identify the site at which activation of protein kinase C (PKC) inhibits arginine vasopressin (AVP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cultured rat inner medullary collecting tubule (RIMCT) cells. Neither endogenous stimulation of PKC by epidermal growth factor (EGF) nor the addition of exogenous 1,2-dioctanoyl-sn-glycerol (DOG) impaired forskolin-stimulated cAMP accumulation. Similarly, neither EGF nor DOG altered cAMP generation in response to cholera toxin. However, pretreatment of RIMCT cells with pertussis toxin resulted in loss of inhibition of AVP-stimulated cAMP accumulation by DOG. Likewise, the ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), to inhibit AVP-stimulated cAMP accumulation was eliminated by pretreatment with pertussis toxin. PMA also inhibited AVP-stimulated adenylyl cyclase activity in plasma membranes prepared from rat inner medullas. In contrast to its effects on AVP, activation of PKC did not impair cAMP accumulation in response to isoproterenol or prostaglandin E2. These studies demonstrate that PKC-mediated inhibition of AVP-stimulated cAMP accumulation in cultured RIMCT cells requires the intact inhibitory guanine nucleotide binding protein Gi.
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PMID:Protein kinase C inhibits arginine vasopressin-stimulated cAMP accumulation via a Gi-dependent mechanism. 838 49

Recent reports have demonstrated that the secretion of ACTH from sheep anterior pituitary primary cultures is markedly stimulated by arginine vasopressin (AVP) but not by CRF, and that AVP-stimulated ACTH secretion is potentiated by CRF. It has also been reported that AVP increases total ACTH content (secreted plus intracellular ACTH), suggesting that AVP stimulates POMC biosynthesis in the ovine anterior pituitary. These observations differ from the rat, in which CRF is the most potent of the ACTH-releasing factors and the only ACTH secretagogue which stimulates POMC gene expression and biosynthesis. The second messenger pathways which mediate CRF- and AVP-stimulated ACTH release (protein kinase A and protein kinase C, respectively) are the same in sheep and rat corticotrophs. The present studies were undertaken to determine if ovine POMC gene expression, unlike the rat POMC gene, is stimulated by AVP via the protein kinase C pathway. A 295 base pair portion of the ovine POMC gene was isolated using polymerase chain reaction and sequenced. Ovine POMC messenger RNA (mRNA) levels were quantitated using this partial complementary DNA clone in a solution hybridization/nuclease protection assay with cytoplasmic RNA from sheep anterior pituitary primary cultures which had been treated with various combinations of ACTH secretagogues or with glucocorticoids for 18 h. Treatment with AVP, alone or with CRF, greatly increased total and secreted ACTH levels; however, the amount of POMC mRNA in these cells was not significantly increased. Treatments which stimulated secretion to a lesser extent and did not alter total ACTH levels (CRF alone, cAMP alone, or with phorbol ester) were associated with a decrease in POMC mRNA levels relative to untreated cells. Glucocorticoid treatment decreased both total ACTH and POMC mRNA levels. Taken together, the data demonstrate a lack of secretagogue-induced stimulation of POMC mRNA levels concomitant with increased total ACTH levels, an unexpected result given the close association between secretion of POMC-derived peptides and POMC gene expression in other mammalian corticotroph systems.
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PMID:Ovine anterior pituitary proopiomelanocortin gene expression is not increased by ACTH secretagogues in vitro. 838 93

We investigated the potential coupling of the Na/H exchanger to protein kinase C (PKC) activation. Mesangial cells (MC), passage 3-8, were exposed to either serotonin (5-HT), arginine vasopressin (AVP), or fibroblast growth factor (FGF). We assessed the effect of these agonists on recovery from an acid load (NH4+/NH3) in the nominal absence of CO2/HCO3. 5-HT, AVP, and FGF significantly enhanced the rate of recovery from 24.2 +/- 4.5 x 10(-4) intracellular pH units/s to 67.7 +/- 5.7, 70.5 +/- 5.1, and 55.7 +/- 6.8, respectively (n > 6, P < 0.0001). The increase in activity was abolished by ethylisopropylamiloride and removal of extracellular Na+, thereby suggesting that activation of Na/H exchanger activity was responsible for enhanced recovery by 5-HT, AVP, and FGF. MC were then pretreated with phorbol ester [phorbol 12-myristate 13-acetate (PMA); 10 microM for 40 h] and acid loaded. 5-HT and AVP did not enhance recovery of PMA-pretreated cells (23.3 +/- 6.8 and 24.9 +/- 4.7, n > 4, not significant), whereas FGF stimulated activity (48.2 +/- 5.5, n > 4, P < 0.001). Similar results were found when MC were pretreated with the PKC antagonist, sphingosine. Specific antibodies were raised against alpha-, beta I-, beta II-, and gamma-isoforms of PKC. We observed that MC express the alpha-, gamma-, and beta I-isoforms, but not the beta II-isoform of PKC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of Na/H exchanger in mesangial cells is associated with translocation of PKC isoforms. 839 24

Primary cultures of neonatal rat cardiomyocytes were pretreated for 16 h with either nonselective (staurosporine, 100 nM) or selective (NPC15437, 20 microM) protein kinase C (PKC) inhibitors. These inhibitors did not affect the basal cytosolic free calcium, [Ca2+]i, level (106 +/- 12 nM) as determined by fura-2 fluorescence methodology. Both agents significantly enhanced the maximal [Ca2+]i responses to endothelin-1 (ET-1) and attenuated the peak [Ca2+]i responses to arginine vasopressin and angiotensin II. They did not alter the EC50 values of any of these agonists. Since depletion of [Ca2+]o led to only partial attenuation of the enhanced response to ET-1 in the treatment groups, it is likely that PKC inhibition results in an exaggerated intracellular mobilization of Ca2+ to ET-1. It is concluded that PKC modulates agonist(s)-evoked intracellular Ca2+ mobilization and that the nature of regulation is governed by the agonist.
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PMID:Protein kinase C inhibitors enhance endothelin-1 and attenuate vasopressin and angiotensin II evoked [Ca2+]i elevation in the rat cardiomyocyte. 842 14

Studies have been performed to investigate the regulation of arginine vasopressin (AVP) mRNA expression in fetal hypothalamic cultures. AVP mRNA-positive neurones were identified by in-situ hybridization histochemistry, and changes in mRNA expression were quantitated by nuclease protection assay. Both protein kinase C and protein kinase A activators increased the expression of AVP mRNA, in contrast to dexamethasone, which inhibited the responses to both protein kinase C and protein kinase A activation.
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PMID:Regulation of arginine vasopressin mRNA in rat fetal hypothalamic cell culture. Role of protein kinases and glucocorticoids. 845 39

Glomerular vasodilatation in the early stages of type I diabetes mellitus apparently results from arteriolar insensitivity to vasoconstrictors. Since cytosolic free calcium ([Ca2+]i) is a major signaling mechanism for smooth muscle contraction, we studied whether growth of smooth muscle-like rat glomerular mesangial cells in media with high glucose concentration affects [Ca2+]i responses to vasoconstrictors. In cells grown for five days in 22 mM glucose, we observed blunted responsiveness to three structurally unrelated vasoconstrictors that elevate [Ca2+]i via a phospholipase C-dependent mechanism, angiotensin II, prostaglandin F2 alpha, and arginine vasopressin. Inhibition of [Ca2+]i responses was not due to an osmotic effect of high glucose, since it was not mimicked by hypertonic mannitol. While the size of intracellular Ca2+ pools was unaffected by elevated glucose, Na+/Ca2+ exchange was markedly inhibited, thus ruling out both impaired filling of Ca2+ stores and enhanced counter-regulatory mechanisms. Impaired myoinositol transport or intracellular sorbitol accumulation were not responsible for the effects of high glucose, since supplementation of media with myo-inositol or with the aldose reductase inhibitor. Alcon 1576, failed to reverse insensitivity to vasoconstrictors. On the other hand, down-regulation or pharmacological inhibition of protein kinase C completely reversed the effects of high glucose, thus indicating involvement of this signal transduction pathway. These data suggest a possible intracellular mechanism for the impaired vascular sensitivity underlying early renal hemodynamic changes in diabetes mellitus.
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PMID:High glucose inhibits cytosolic calcium signaling in cultured rat mesangial cells. 845 57


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