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)

Osmotic water permeability (Pf) in toad bladder is regulated by the vasopressin (VP)-dependent movement of vesicles containing water channels between the cytoplasm and apical membrane of granular cells. Apical endosomes formed in the presence of serosal VP have the highest Pf of any biological or artificial membrane (Shi and Verkman. 1989. J. Gen. Physiol. 94:1101-1115). We examine here: (a) the influence of protein kinase A and C effectors on transepithelial Pf (Pfte) in intact bladders and on the number and Pf of labeled endosomes, and (b) whether endosome Pf can be modified physically or biochemically. In paired hemibladder studies, Pfte induced by maximal serosal VP (50 mU/ml, 0.03 cm/s) was not different than that induced by 8-Br-cAMP (1 mM), forskolin (50 microM), VP + 8-Br-cAMP, or VP + forskolin. Pf was measured in endosomes labeled in intact bladders with carboxyfluorescein by a stopped-flow, fluorescence-quenching assay using an isolated microsomal suspension; the number and Pf (0.08-0.11 cm/s, 18 degrees C) of labeled endosomes was not different in bladders treated with VP, forskolin, and 8-Br-cAMP. Protein kinase C activation by 1 microM mucosal phorbol myristate acetate (PMA) induced submaximal bladder Pfte (0.015 cm/s) and endosome Pf (0.022 cm/s) in the absence of VP, but had little effect on maximal Pfte and endosome Pf induced by VP. However, PMA increased by threefold the number of apical endosomes with high Pf formed in response to serosal VP. Pf of endosomes containing the VP-sensitive water channel decreased fourfold by increasing membrane fluidity with hexanol or chloroform (0-75 mM); Pf of phosphatidylcholine liposomes (0.002 cm/s) increased 2.5-fold under the same conditions. Endosome Pf was mildly pH dependent, strongly inhibited by HgCl2, but not significantly altered by GTP gamma S, Ca, ATP + protein kinase A, and phosphatase action. We conclude that: (a) water channels cycled in endocytic vesicles are functional and not subject to physiological regulation, (b) VP and forskolin do not have cAMP-independent cellular actions, (c) activation of protein kinase C stimulates trafficking of water channels, but does not increase the number of apical membrane water channels induced by maximal VP, and (d) water channel function is sensitive to membrane fluidity. By using VP and PMA together, large quantities of endosomes containing the VP-sensitive water channel are labeled with fluid-phase endocytic markers.
J Gen Physiol 1990 Oct
PMID:Regulation of the formation and water permeability of endosomes from toad bladder granular cells. 197 9

The effect of transient cerebral ischemia and intraventricular injection of kainic acid on adenylate cyclase and protein kinase C as labeled by [3H]forskolin ([3H]FOR) and [3H]phorboldibutyrate ester ([3H]PDBU) in several rat brain microregions was investigated in a quantitative autoradiographic study. Four days after transient four vessel occlusion a 80% loss of [3H]FOR and a 35% loss of [3H]PDBU binding could be measured in the CA1 stratum radiatum of operated Wistar rats as compared to control rats. Four days after intraventricular injection of kainic acid only a marginal loss of [3H]FOR and a 30% increase of [3H]PDBU binding was seen in the CA1 stratum radiatum while in the CA3 stratum lucidum and radiatum respectively a 30% loss of [3H]FOR and no significant change in [3H]PDBU binding was observed. As transient cerebral ischemia and intraventricular kainic acid injection are depleting the hippocampal CA1 region of CA1 pyramidal cells and axons of CA3 pyramidal cells respectively in rat brain, these findings strongly suggest that both adenylate cyclase and protein kinase C are localized in CA1 pyramidal cells of rat hippocampus.
J Neural Transm Gen Sect 1991
PMID:Post- and presynaptic lesions in the CA1 region of hippocampus: effect on [3H]forskolin and [3H]phorboldibutyrate ester binding. 203 10

1. CGS 9343B is a novel, potent and selective inhibitor of calmodulin activity, which unlike other known calmodulin antagonists, does not inhibit protein kinase C activity and does not possess potential antidopaminergic activity. Here we show that CGS 9343B, like other calmodulin antagonists reported previously, is most effective in treatment of burns. 2. The effectiveness of CGS 9343B on skin burns was evaluated by electron microscopic studies, as well as by measurements of hemoglobin, ATP and enzymes which are markedly changed in the burned skin. 3. As CGS 9343B is a more selective probe for calmodulin function than other inhibitors, the similarity of its effects on burns to that of other calmodulin antagonists, strongly suggest that their action on burns is mediated through calmodulin inhibition.
Gen Pharmacol 1991
PMID:Effect of the calmodulin antagonist CGS 9343B on skin burns. 205 Feb 88

The major immediate early enhancer of human cytomegalovirus (HCMV) is known to exert a strong constitutive transcription stimulation in a broad spectrum of cells. This basal activity can be augmented considerably by elevated levels of intracellular cAMP in a cell type-specific manner. Cyclic AMP induction was observed in several lymphoid cell lines and in HeLa cells. One of the functionally important enhancer sequence modules, the 19 bp repeat element, mediates this effect as a cAMP-responsive element (CRE). It acts more efficiently than the corresponding sequence from the human chorionic gonadotropin gene. It is suggested that protein kinase C is involved in the pathway which leads to the activation of CRE-containing genes in lymphoid cells. Gel retardation assays indicated that similar, but not identical complexes are formed between nuclear protein extracts and the CREs of HCMV and the gonadotropin gene.
J Gen Virol 1990 Jan
PMID:Cell type-specific induction of the major immediate early enhancer of human cytomegalovirus by cyclic AMP. 215 28

Induction of interferon-beta (IFN-beta) in human (BG-9), simian (CV-1) and mouse (L-929) cell lines by Sendai virus and by poly(rI). poly(rC) has been studied for its possible dependence on protein kinase C (PKC) through the use of pharmacological inhibitors (K252a and H-7) of PKC. Exposure of BG-9, CV-1 or L-929 cells to K252a (greater than or equal to 0.025 microM), a staurosporine derivative, 24 h before or after induction of IFN with poly(rI).poly(rC), inhibited by greater than 95% the production of IFN-beta. In contrast, virus-induced IFN production was enhanced threefold or more by K252a in BG-9 and L-929 but not in CV-1 cells. A naphthalene sulphonamide inhibitor of PKC, H-7, at greater than or equal to 5 microM, decreased poly(rI).poly(rC)-induced IFN production in BG-9 and CV-1 cells by 75 to 94%, but had no effect on IFN production in L-929 cells. Viral induction of IFN was not affected significantly by H-7 in BG-9, CV-1 and L-929 cells. In contrast to these results, the calmodulin inhibitor, trifluoperazine (5 to 15 microM) did not affect IFN-beta production by poly(rI).poly(rC) but significantly enhanced IFN production by Sendai virus in both human and murine cell lines. Thus, in human and simian fibroblasts the induction of IFN-beta by poly(rI).poly(rC) appears to be PKC-dependent, whereas viral induction of IFN-beta is not. Results with K252a implicate PKC in non-viral induction of IFN in mouse fibroblasts, as well. Direct measurements of PKC activity in BG-9 cells exposed to several concentrations of K252a showed that the membrane PKC activity is significantly more sensitive to inhibition by K252a than is cytosolic PKC activity. In L-929 cells, K252a inhibited membrane PKC activity similarly, but was less effective as an inhibitor of cytosolic enzyme activity than in BG-9. These studies support an integral role for PKC activity, particularly membrane-associated activity, in non-viral [poly(rI).poly(rC)] induction of IFN-beta in human, simian and mouse fibroblasts.
J Gen Virol 1990 Dec
PMID:Effect of protein kinase C inhibitors on interferon-beta production by viral and non-viral inducers. 217 82

1. Aim of the present investigation was to investigate the effects of calcium blocking agent diltiazem on human platelet response to aggregating agents. 2. Results showed that diltiazem inhibits platelet aggregation induced by ADP, arginine vasopressin, adrenaline, collagen, Na arachidonate, thrombin and phorbol ester PMA in a dose-dependent way. 3. Diltiazem decreased also beta-thromboglobulin release and Thromboxane B2 production from stimulated platelets. 4. Intraplatelet cyclic AMP levels were not modified by the substance. 5. Data provide evidence that the modulation of human platelet function by diltiazem could be also related to inhibition of protein kinase C.
Gen Pharmacol 1990
PMID:Studies on inhibition of human platelet response by diltiazem. 227 94

Measurements of cytosolic pH (pHi) 36Cl fluxes and free cytosolic Ca2+ concentration ([Ca2+]i) were performed in the clonal osteosarcoma cell line UMR-106 to characterize the kinetic properties of Cl-/HCO3- (OH-) exchange and its regulation by pHi and [Ca2+]i. Suspending cells in Cl(-)-free medium resulted in rapid cytosolic alkalinization from pHi 7.05 to approximately 7.42. Subsequently, the cytosol acidified to pHi 7.31. Extracellular HCO3- increased the rate and extent of cytosolic alkalinization and prevented the secondary acidification. Suspending alkalinized and Cl(-)-depleted cells in Cl(-)-containing solutions resulted in cytosolic acidification. All these pHi changes were inhibited by 4',4',-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) and H2DIDS, and were not affected by manipulation of the membrane potential. The pattern of extracellular Cl- dependency of the exchange process suggests that Cl- ions interact with a single saturable external site and HCO3- (OH-) complete with Cl- for binding to this site. The dependencies of both net anion exchange and Cl- self-exchange fluxes on pHi did not follow simple saturation kinetics. These findings suggest that the anion exchanger is regulated by intracellular HCO3- (OH-). A rise in [Ca2+]i, whether induced by stimulation of protein kinase C-activated Ca2+ channels, Ca2+ ionophore, or depolarization of the plasma membrane, resulted in cytosolic acidification with subsequent recovery from acidification. The Ca2+-activated acidification required the presence of Cl- in the medium, could be blocked by DIDS, and H2DIDS and was independent of the membrane potential. The subsequent recovery from acidification was absolutely dependent on the initial acidification, required the presence of Na+ in the medium, and was blocked by amiloride. Activation of protein kinase C without a change in [Ca2+]i did not alter pHi. Likewise, in H2DIDS-treated cells and in the absence of Cl-, an increase in [Ca2+]i did not activate the Na+/H+ exchanger in UMR-106 cells. These findings indicate that an increase in [Ca2+]i was sufficient to activate the Cl-/HCO3- exchanger, which results in the acidification of the cytosol. The accumulated H+ in the cytosol activated the Na+/H+ exchanger. Kinetic analysis of the anion exchange showed that at saturating intracellular OH-, a [Ca2+]i increase did not modify the properties of the extracellular site. A rise in [Ca2+]i increased the apparent affinity for intracellular OH- (or HCO3-) of both net anion and Cl- self exchange. These results indicate that [Ca2+]i modifies the interaction of intracellular OH- (or HCO3-) with the proposed regulatory site of the anion exchanger in UMR-106 cells.
J Gen Physiol 1990 Jan
PMID:Cytosolic pH regulation in osteoblasts. Regulation of anion exchange by intracellular pH and Ca2+ ions. 229 28

1. Field electrical stimulation induced tritium release from cat cerebral arteries preincubated with [3H]serotonin (5-HT). 2. This release was markedly reduced by tetrodotoxin (0.8 microM), B-HT 920 (1 microM), denervation with 6-OH-dopamine (6-OHDA) and OCa2+, and increased by phentolamine (1 microM) and phorbol 12,13-dibutyrate (1 and 3 microM). 3. 5-HT (10 and 100 microM) and NA (0.1, 1 and 10 microM) caused concentration-dependent tritium release in control arteries, but not in those denervated with 6-OHDA. 4. [3H]5-HT uptake was greatly reduced by preincubation of arteries with cocaine (10 microM), ouabain (100 microM) or denervation with 6-OHDA. 5. 5-HT did not amplify contractions elicited by noradrenaline (NA) in middle cerebral arteries. 6. These data indicate: (1) 5-HT is mainly accumulated in adrenergic nerve endings; (2) 5-HT release is modulated by presynaptic alpha 2-adrenoceptors; (3) protein kinase C of perivascular adrenergic nerve endings participates in 5-HT release, and (4) 5-HT did not amplify NA responses.
Gen Pharmacol 1990
PMID:[3H]5-hydroxytryptamine uptake and release in cat cerebral arteries. 233 39

The ontogeny of phorbol ester receptors, which have been considered to correspond to protein kinase C, in the rat brain was studied through in vitro autoradiography with 3H-phorbol 12,13-dibutyrate (3H-PDBu). The distribution of 3H-PDBu binding sites in the adult rat brain was similar to the previous reports by other researchers. The developmental pattern of 3H-PDBu binding sites varied with brain region. 3H-PDBu binding sites in the amygdala, thalamus, stratum pyramidale of CA 1 of the hippocampus, dentate gyrus, superior colliculus, substantia nigra, interpeduncular nucleus and cerebellar molecular layer were postnatally increased to adult levels and after that they remained constant. On the other hand, in the stratum oriens and stratum radiatum of CA 1 of the hippocampus, and in the lateral and medial geniculate bodies, 3H-PDBu binding sites reached peaks at 21 or 28 days of postnatal age and after that they declined to adult levels. The cerebellar granular layer showed a low level of 3H-PDBu binding sites throughout all the ontogenetic stages. A distinct ontogenetic pattern of phorbol ester receptors in various regions of the brain may reflect a role of protein kinase C in the neural development of each discrete area.
J Neural Transm Gen Sect 1990
PMID:Ontogeny of phorbol ester receptors in rat brain studied by in vitro autoradiography. 235 27

1. An investigation was made of the effects of phorbol esters, 12-O-tetradecanoylphorbol acetate (TPA) and secretin on pancreatic juice secretion in the anaesthetized rat. TPA (10(-12)-10(-8) mol/kg body wt) evoked marked dose-dependent increases in secretory rate and total protein output. 2. An inactive phorbol ester (4 alpha-phorbol-12-13-didecanoate; 4 alpha PDD) had no effect on the secretory rate but increased total protein output compared to saline control animals. 3. When TPA was administered in combination with the protein kinase C inhibitor, Polymyxin B (10(-8) mol/kg body wt) both secretory rate and protein output were significantly reduced (P less than 0.001) compared to TPA alone. 4. Secretin (50-1600 pmol/kg body wt) increased both pancreatic juice flow and total protein output in a dose-dependent manner. 5. Simultaneous administration of secretin (50-1600 pmol/kg body wt) and TPA (10(-10) mol/kg body wt) resulted in a marked attenuation in the secretin-induced secretory rate while secretin-evoked protein output was unaffected. 6. The results indicate that protein kinase C activation is associated with pancreatic juice secretion and it may also modulate secretin-induced pancreatic juice flow in the anaesthetized rat.
Gen Pharmacol 1990
PMID:Effects of phorbol esters and secretin on pancreatic juice secretion in the anaesthetized rat. 237


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