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 influence of the renin-angiotensin system on the control of cell communication was investigated in isolated ventricular cell pairs of adult rats. It was found that angiotensin II (1 microgram/ml) reduced the junctional conductance (gj) by about 55% within 20 s. This effect of angiotensin II was suppressed by DuP 753--an angiotensin receptor blocking agent. Enalapril (1 microgram/ml)--an angiotensin converting enzyme inhibitor--caused an increase in junctional conductance (106%) within 2 min. The effect of enalapril on gj was not related to activation of beta-adrenergic receptors or cAMP-dependent protein kinase. The effect of angiotensin II on gj was suppressed by staurosporine--a potent inhibitor of protein kinase C. This finding indicates that the peptide is changing gj through activation of protein kinase C. The increase in cell coupling caused by enalapril raises the possibility that the antiarrhythmic action of enalapril as well its effect in congestive heart failure are related to an increase in electrical synchronization of cardiac myocytes.
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PMID:The role of the renin-angiotensin system in the control of cell communication in the heart: effects of enalapril and angiotensin II. 128 Jul 22

In vascular smooth muscle cell (VSMC) cultures from Sprague-Dawley (SD) and hypertensive transgenic rats for the mouse renin gene Ren-2 (TGR), the DNA synthesis, which was analyzed by the uptake of [3H]thymidine, was higher in TGR than SD VSMCs (2.5- to 8-fold, mean of 5.6-fold) under basal conditions. DNA synthesis was increased by fetal calf serum (10%) in SD cells more than in TGR VSMCs, and was decreased by heparin (400 micrograms/ml) and by phorbol-12,13-dibutyrate (10(-7) M) in TGR VSMCs to a higher degree than in SD cells. Neither endothelin (10(-7) M), angiotensinogen (10(-8) M), the renin inhibitor CGP 29,287 (10(-4) M), angiotensin I (10(-7) M), captopril (10(-5) M), angiotensin II (10(-7) M), nor saralasin (10(-6) M) modified DNA synthesis in either type of VSMCs. Sodium nitroprusside (10(-4) and 10(-3) M) increased DNA synthesis in both kinds of VSMCs but in TGR cultures it became toxic at 10(-3) M. 8-Bromocyclic GMP (10(-7) to 10(-5) M) reduced DNA synthesis in SD cells more than in TGR VSMCs. These results suggest that (a) cellular mechanisms of proliferation appear to be more activated in TGR VSMCs, likely involving a protein kinase C-dependent pathway but not the renin-angiotensin system, and (b) in both type of cells, sodium nitroprusside possesses proliferative properties whereas 8-bromocyclic GMP has antiproliferative properties.
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PMID:Vascular smooth muscle proliferation in hypertensive transgenic rats. 128 47

In this study we examined the effects of classic second messenger molecules on renin secretion and renin synthesis in primary cultures of mouse renal juxtaglomerular (JG) cells. Stimulation of cAMP formation by forskolin, inhibition of calmodulin by calmidazolium, and inhibition of Na+/H+ exchange by ethylisopropylamiloride enhanced renin secretion. Raising of intracellular cGMP by 8-bromo-cGMP and activation of protein kinase C by phorbol ester led to an inhibition of secretion. Renin synthesis was stimulated by forskolin. Calmidazolium, EIPA, 8-bromo-cGMP, and phorbol ester were without effect on basal renin synthesis. The data suggest that renin secretion is influenced by a number of transmembrane transduction systems which in their majority exert a negative control on renin secretion. Activation of adenylate cyclase appears to be a stimulatory control mechanism for both the secretion and the synthesis of renin. The findings suggest, moreover, that the second messenger controls of renin secretion and renin synthesis are not strictly linked in renal JG cells.
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PMID:Determinants of renin secretion and renin synthesis in isolated mouse juxtaglomerular cells. 165 64

The possible roles of cyclic AMP and protein kinase C in the release of renin from human decidual cells were investigated by examining renin release from monolayers of decidual cells exposed for 72 h to agents that increase intracellular cAMP or activate protein kinase C. Dibutyryl cAMP (10-1000 microM caused a dose-dependent stimulation of renin release after a 24-h exposure. Maximal stimulation, 410 per cent greater than that of control cells, occurred at 72 h, and 98 per cent of the renin released into the medium was in the form of prorenin. Forskolin (10-1000 microM) and cholera toxin (CT. 20-1000 ng/ml), both of which stimulate adenyl cyclase, also stimulated prorenin release. Phorbol myristate acetate (PMA), an activator of protein kinase C, had little effect on basal prorenin release at 100 nM but potentiated the stimulation of prorenin release by cAMP and CT. The effects on prorenin release were paralleled by stimulation of active renin release. The results of this study therefore implicate cAMP and protein kinase C in the regulation of prorenin release from decidual cells and suggest that prorenin release from the decidua and other tissues is regulated by the same second messengers.
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PMID:Cyclic AMP as a second messenger for prorenin release from human decidual cells. 166 20

This study was designed to evaluate the contribution of calmodulin and protein kinase C to renin release from isolated glomeruli of spontaneously hypertensive rats (SHR, Okamoto and Aoki). Male 7-week-old SHR and age-matched control Wistar-Kyoto rats (WKY) were used in this study. Isolated glomeruli were sealed in the superfusion chamber and perfused with Krebs-Ringer solution at a constant flow of 0.3 mL/min. Renin release was increased by calmodulin inhibitor, W-7, and protein kinase C inhibitor, H-7, in both SHR and WKY. SHR showed higher maximal levels of renin release by W-7 and lower maximal levels by H-7 compared to WKY. These results indicate that calmodulin and protein kinase C play inhibitory roles in renin release from juxtaglomerular cells. The calmodulin-mediated suppression mechanism in renin release appears to be augmented in the SHR, whereas the protein kinase C-mediated system is attenuated.
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PMID:Contribution of calmodulin and protein kinase C to renin release in spontaneously hypertensive rats. 222 69

In this report, we have described a serum free culture method for culturing bovine theca cells in vitro. These cultured cells could be stimulated with LH to produce renin and prorenin. Though intracellular prorenin as well as renin was increased by LH, no renin was found to be released into the extracellular medium. The extracellular medium contained prorenin exclusively. The stimulatory effect of LH could be mimicked by 8-bromo-cAMP (8-Br-cAMP) and forskolin, suggesting cAMP to be the second messenger involved. Induction of renin and prorenin production by LH in cultured theca cells was dependent upon de novo protein synthesis, since the action of LH could be completely blocked by the protein synthesis inhibitor, cycloheximide. The stimulatory effects of LH, 8-Br-cAMP, or forskolin were also blocked by 4 beta-phorbol 12-myristate 13-acetate (PMA), via putative activation of protein kinase C. However, to completely block the stimulatory effect of LH or 8-Br-cAMP, it was necessary to add PMA either before LH/8-Br-cAMP was added or simultaneously with the agonists. With progressive delay in addition of PMA after LH/8-Br-cAMP was added, the extent of inhibition decreased gradually and if PMA was added anytime after 4 h of LH/8-Br-cAMP addition, no inhibitory effect could be observed. Thus we have shown that renin/prorenin production by theca cells in vitro can be directly regulated by LH in a cAMP-dependent manner. Prorenin is preferentially released from the cells. Activation of protein kinase C appears to inhibit some very early steps in the induction of prorenin/renin production which however is distal to cAMP formation.
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PMID:Inhibitory effects of a tumor-promoting phorbol ester on luteinizing hormone-stimulated renin and prorenin production by cultured bovine theca cells. 222 8

1. The present experiments were designed to determine the effect of melittin on renin secretion. Melittin is a polypeptide component of bee venom which stimulates phospholipase A2 activity, thereby increasing arachidonic acid release and prostaglandin (PG) synthesis, and which inhibits protein kinase C activity. Either of these actions might be expected to stimulate renin secretion, since renin secretion is stimulated by arachidonic acid and by several PGs, and since renin secretion is inhibited by several activators of protein kinase C. 2. In rat renin cortical slices incubated at 37 degrees C in a buffered and oxygenated physiological saline solution, 0.1-10 microM-melittin produced a concentration-dependent stimulation of both prostaglandin E2 (PGE2) synthesis and renin secretion. However, melittin-stimulated renin secretion is independent of melittin-stimulated phospholipase A2 activity, arachidonic acid release, and PG synthesis, since 20 microM-quinacrine (a phospholipase A2 antagonist) and 50 microM-meclofenamate (a cyclooxygenase antagonist) antagonized basal and melittin-stimulated PGE2 synthesis but had no effects on basal or melittin-stimulated renin secretion. 3. Furthermore, melittin-stimulated renin secretion is not produced by inhibition of protein kinase C, since an activator of protein kinase C (12-O-tetradecanoylphorbol 13-acetate, TPA), enhanced rather than antagonized melittin-stimulated renin secretion. Ouabain partially antagonized, but did not completely block, melittin-stimulated renin secretion. 4. Thus, melittin-stimulated phospholipase A2 activity probably accounts for stimulated PGE2 production, but not for stimulated renin secretion. The mechanism of melittin-stimulated renin secretion is unclear; an effect on protein kinase C does not appear to be involved, and in contrast to the stimulatory effects of a variety of other substances, melittin-stimulated renin secretion is only partially antagonized by ouabain.
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PMID:Effect of melittin on renin and prostaglandin E2 release from rat renal cortical slices. 223 11

Modulation of renin synthesis by lipoxygenase products has been studied in cultured human mesangial cells under basal conditions and in the presence of prostaglandin (PG) E2. Total renin and cyclic AMP productions were stimulated in a dose-dependent manner (0.1-10 microM) by PGE2. The stimulatory effect of PGE2 on renin production was inhibited by 12-hydroxyeicosatetraenoic acid (12-HETE) between 0.1 and 100 nM. Extracellular and intracellular renin were affected similarly. Neither basal and PGE2-dependent cyclic AMP nor basal cyclic GMP productions were modified. 15-Hydroxyeicosatetraenoic acid (15-HPETE), 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 15-hydroperoxyeicosatetraenoic acid (15-HPETE) had the same effects as 12-HETE. Intracellular calcium concentration was not modified in the presence of 12-HETE. Since oleyl-2-acetylglycerol (OAG), an analog of diacylglycerol, also inhibited PGE2-stimulated renin production, it is hypothesized that the effect of the lipoxygenase products is mediated via protein kinase C stimulation.
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PMID:Modulation of renin synthesis by lipoxygenase products in cultured human mesangial cells. 254 91

The intracellular messengers that seem to be involved in renin secretion (RS) from juxtaglomerular cells (JG) are calcium (Ca), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Unlike the majority of secretory systems, an increase in intracellular Ca concentration and calmodulin and protein kinase C activation inhibit RS. The intracellular Ca concentration in JG cells can be modified if: 1) the normal mechanisms of Ca extrusion of these cells is altered; 2) the calcium output is blocked by lanthanum; 3) the function of the voltage-sensitive Ca-channels is modified; 4) uptake or liberation of Ca from endoplasmic reticulum is modified; 5) plasmatic membrane is bypassed with calcium ionophores such as A 23187. 6) JG cells are stimulated by hormones that increase Ca and activate protein kinase C such as angiotensin II, vasopressin or alpha-1 adrenergic agonists; 7) extracellular Ca concentration increases or decreases. RS is stimulated by dibutyryl cAMP, cAMP phosphodiesterase inhibitors and by hormones and agents that activate adenylate cyclase (beta adrenergic agonists, bradykinin, histamine, forskolin and ethylcarboxamide adenosine). On the contrary, RS is inhibited by hormones and agents that inhibit adenylate cyclase such as: alpha-2 adrenergic agonists, neuropeptide Y, angiotensin II and cyclohexyladenosine. Pertussis toxin increases basal RS, blocks the inhibition by agents and hormones which inhibit adenylate cyclase and potentiate the stimulation produced by beta-adrenergic agonists. In JG cells, atrial natriuretic peptide inhibits RS, increases cGMP and decreases cAMP. The increase in cGMP correlates well with the inhibition of RS.
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PMID:[Intracellular messengers in the regulation of renin secretion]. 255 Oct 26

In the isolated perfused rat kidney, endothelin inhibits renin release and reduces the renal perfusate flow. The half-maximally effective concentrations were 30 and 50 pmol/l, respectively. Both effects are slow in onset and in washout. The calcium channel antagonist nimodipine (2 mumol/l) completely blocks the vasoconstrictor and renin secretion response of a median inhibitory concentration (IC50) of endothelin, indicating that entry of external calcium may play a role. Vasoconstriction and inhibition of renin release by endothelin are attenuated in the presence of a protein kinase C inhibitor, staurosporine, which suggests that protein kinase C helps to mediate the effects of endothelin on renin secretion and vascular resistance.
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PMID:The effects of endothelin on renovascular resistance and renin release. 269 38


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