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)

Slices of rat hippocampus, preincubated with [3H]norepinephrine ([3H]NE), were superfused and stimulated by addition of 3,4-diaminopyridine (3,4-DAP) for 10 min to the superfusion medium. 3,4-DAP-evoked [3H]NE release both in the absence and presence of extracellular Ca2+. 3,4-DAP-evoked Ca(2+)-independent release of [3H]NE was highly sensitive to sodium channel blocker, tetrodotoxin (TTX, 100% inhibition), suggesting that Na+ per se entered into nerve terminals but not depolarization of membrane followed by Ca2+ channel opening is necessary for 3,4-DAP-evoked Ca(2+)-independent release of [3H]NE. Phorbol ester PDB increased by 480% of control and polymyxin B (PMB) decreased 3,4-DAP-evoked [3H]NE release by 94% of control in the absence of extracellular Ca2+ indicating that the alterations of voltage-dependent Ca(2+)-currents into the cells are not involved in the mechanism of the modulation of 3,4-DAP-evoked [3H]NE release by protein kinase C.
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PMID:[3,4-Diaminopyridine-evoked norepinephrine release from hippocampal in the absence of extracellular calcium]. 131 33

Regulation of the avidity of LFA-1 (CD11a/CD18, alpha L beta 2) for its ligand ICAM-1 (CD54) was studied in human B cells by evaluating the effects of a phorbol ester, anti-IgM antibodies, staurosporine, and okadaic acid. We monitored changes in LFA-1 avidity by quantifying binding of cells to an immobilized rICAM-1 fusion protein. In this assay, the protein kinase C-activating phorbol ester PDB and anti-IgM antibodies, as well as the protein kinase inhibitor, staurosporine, were able to induce LFA-1-dependent binding to ICAM-1. This demonstrates that the high avidity state of LFA-1 can be induced by a protein kinase C-dependent and by a protein kinase C-independent pathway. Furthermore, treatment of the cells with the protein phosphatase inhibitor, okadaic acid, inhibited binding to ICAM-1. Treatment with staurosporine before addition of okadaic acid not only induced enhanced binding of cells to ICAM-1, but also dramatically reduced the ability of okadaic acid to inhibit binding. These results suggest a critical role for a protein phosphatase in inducing the high avidity state of LFA-1 as well as a role for a protein kinase in inducing the low avidity state of LFA-1.
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PMID:Regulation of LFA-1 avidity in human B cells. Requirements for dephosphorylation events for high avidity ICAM-1 binding. 135 24

The heat-stable enterotoxin of Escherichia coli (STa) stimulates membrane-bound guanylate cyclase in intestinal epithelium and induces fluid and ion secretion. Using the T84 human colon carcinoma cell line as a model, we observed that phorbol esters markedly enhanced STa-stimulated cyclic GMP accumulation in T84 cells (C. S. Weikel, C. L. Spann, C. P. Chambers, J. K. Crane, J. Linden, and E. L. Hewlett, Infect. Immun. 58:1402-1407, 1990). In this study we document that the phorbol ester treatment increases 125I-STa-binding sites as well as membrane-bound guanylate cyclase activity in T84 cells and provide evidence that both effects are mediated by phosphorylation. Guanylate cyclase activity was increased approximately 50% in membranes prepared from intact T84 cells treated with phorbol-12,13-dibutyrate (beta-PDB) and after treatment of homogenates with beta-PDB in a manner dependent on ATP, MgCl2, and cytosol. Similarly, treatment of membranes with purified bovine brain protein kinase C in the presence of appropriate cofactors and beta-PDB resulted in an increase in STa-stimulated guanylate cyclase activity of about 70%. Likewise, the number of 125I-STa-binding sites was increased by about 25 to 40% in membranes prepared from intact cells or homogenates treated with beta-PDB; no effect on binding affinity (Kd = 0.15 nM) was noted. These experiments suggest that protein kinase C may phosphorylate the STa receptor-guanylate cyclase or a closely related protein and increase guanylate cyclase activity. The stimulatory effects of protein kinase C on STa-sensitive guanylate cyclase are opposite in direction to the profound inhibitory effects of the kinase on atrial natriuretic peptide-stimulated guanylate cyclase, demonstrating differential regulation by protein kinases within the guanylate cyclase-receptor family.
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PMID:Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) and protein kinase C. 136 Apr 49

The involvement of protein kinase C (PKC) in the regulation of intestinal ion secretion was studied in polarized monolayers of the HT29cl.19A human colon carcinoma cell line. Carbachol, phorbol esters [PMA (phorbol 12-myristate 13-acetate) and PDB (phorbol 12,13-dibutyrate)] and 8-bromo cyclic AMP (8-Br-cAMP) induced Cl secretion, as measured by a rise in the short-circuit current (ISC). The electrical response to carbachol coincided with a transient translocation of PKC alpha from the soluble to the particulate fraction. The carbachol-, PDB- and 8-Br-cAMP-induced ISC responses were inhibited by pretreatment of the cells with PMA (0.5 microM) for 2 h, a time period in which PKC alpha, beta 1 and gamma levels were not changed. As shown by 86Rb+ and 125I- efflux studies, the main targets for this inhibition were basolateral K+ transporters rather than apical Cl- channels. Prolonged exposure to PMA (24 h) led to a 60% recovery of the 8-Br-cAMP response, but not of the carbachol- or PDB-provoked secretion. As shown by immunoblotting with PKC-isoenzyme-specific antisera, the recovery of the 8-Br-cAMP response coincided with the down-regulation of PKC alpha, whereas the levels of PKC beta 1 and gamma were unmodified. These results suggest that PKC alpha, but not PKC beta 1 or gamma, is involved in both acute stimulation and chronic inhibition of ion secretion in the HT29cl.19A colonic cell line.
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PMID:Dual role for protein kinase C alpha as a regulator of ion secretion in the HT29cl.19A human colonic cell line. 163 59

The question was studied whether there is a direct link between protein kinase C and presynaptic alpha-2 adrenoceptors regulating depolarization-induced norepinephrine (NE) release. Effects of the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (4 beta-PDB) on electrically evoked [3H]NE release were investigated in rabbit and rat hippocampus. Release evoked with 4 pulses/100 Hz (POP stimulation; i.e. under conditions virtually free of autoinhibition), was increased by 4 beta-PDB in a comparable manner in both species. Conversely, the alpha-2 adrenoceptor agonist clonidine diminished POP-induced [3H]NE release in a concentration-dependent manner. The net effects of clonidine were of a similar magnitude up to near maximal concentrations, irrespective of whether or not the 4 beta-PDB was present. Correspondingly, the net effect of 4 beta-PDB remained unchanged under these conditions. An impairment of the net effect of 4 beta-PDB was only seen at higher concentrations of clonidine. Concurrent addition of the alpha-2 adrenoceptor antagonist yohimbine and 4 beta-PDB enhanced release elicited with 36 pulses/3 Hz (i.e., in presence of autoinhibition), in a manner which was at least additive. Taken together, the above data exclude a direct link between presynaptic alpha-2 adrenoceptors and protein kinase C and restrict a functional interaction to very distinctive conditions.
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PMID:A detailed study on the effects of protein kinase C activation on alpha-2 adrenoceptor-coupled modulation of norepinephrine release in hippocampus. 164 91

The membrane electrical parameters and component conductances of rat extensor digitorum longus muscle fibres were studied in vitro at 30 degrees C with standard two microelectrode square pulse cable analysis in the presence of protein kinase C (PKC) activators and inhibitors. The PKC activator, 4-beta-phorbol-12,13 dibutyrate (4-beta-PDB), (2-90 nM) blocked up to 67% chloride conductance (GCl) in rat skeletal muscle fibres and induced myotonic hyperexcitability. The concentration necessary to produce a 50% block of the membrane GCl was 23 nM. The "inactive" 4-alpha-phorbol-12,13 dibutyrate had no effect at 2 microM. The blocking effect of 4-beta-PDB on GCl was prevented by preincubation of the preparations with the PKC inhibitors, staurosporine (1-5 microM) and tetrahydropapaverolone (50-100 microM). The blocking effects on membrane GCl of 4-beta-PDB and its antagonism by the inhibitors used support the concept of the involvement of PKC in regulating Cl channels of mammalian skeletal muscle fibres.
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PMID:Modulation of rat skeletal muscle chloride channels by activators and inhibitors of protein kinase C. 165 45

Slices of rat hippocampus, preincubated with [3H]noradrenaline [(3H]NA), were superfused continuously and stimulated by addition of 3,4-diaminopyridine (3,4-DAP; 100 microM) for 10 min to the superfusion medium. An overflow of 3H evoked by 3,4-DAP (representing [3H]NA release) was measurable not only in the presence but also in the absence of extracellular Ca2+. Both the protein kinase C (PKC) activator 4 beta-phorbol 12,13-dibutyrate (4 beta-PDB) and the PKC inhibitor polymyxin B, affected mainly the evoked release in the absence of extracellular Ca2+ in a facilitatory or inhibitory manner, respectively. Moreover, in the absence of extracellular Ca2+, both the 3,4-DAP-evoked [3H]NA release and the facilitatory effect of 4 beta-PDB were abolished in the presence of tetrodotoxin or in the absence of Na+ in the superfusion medium. Ruthenium red, a blocker of mitochondrial Ca2+ reuptake, potently increased 3,4-DAP-evoked [3H]NA release in Ca(2+)-free EGTA-containing medium. The facilitatory effects of ruthenium red and 4 beta-PDB were additive. From these and earlier observations we conclude (1) that the mechanism of 3,4-DAP-evoked [3H]NA release involves both Ca2+ influx into the nerve terminals and mobilization of intraneuronal Ca2+ pools. Most probably Ca2+ release from cytoplasmic Ca2+ stores (e.g. endoplasmic reticular pools or mitochondria) is induced by Na+ ions entering the nerve endings during 3,4-DAP-evoked repetitive action potentials. (2) The facilitatory effect of phorbol ester on 3,4-DAP-evoked NA release appears to be mediated not by changes in Ca2+ influx, but by enhancement of intraneuronal events distal to Na+ ion entry and increased intracellular Ca2+ availability.
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PMID:3,4-Diaminopyridine-evoked noradrenaline release in rat hippocampus: role of Na+ entry on Ca2+ pools and of protein kinase C. 171 65

Cholecystokinin (CCK) is a potent neuropeptide hormone with activity on various gastrointestinal organs during the digestive process. It was recently suggested that CCK may also act on the immune system. In this study we investigated the effect of CCK on the human mucosal immune system as represented by colonic lamina propria lymphocytes (LPL). Our results demonstrated that CCK at concentrations of 10(-13) M to 10(-7) M inhibits thymidine incorporation into Con A-stimulated LPL DNA by up to 40%. Moreover, this inhibitory effect was reversed by the specific CCK receptor antagonist, L-364718, at concentrations of 10(-8) M to 10(-5) M. In addition, CCK did not affect DNA synthesis of LPL stimulated with phorbol ester (PDB) and calcium ionophore (ionomycin). It is postulated that the CCK effect may involve intracellular metabolic steps proximal to protein kinase C activation and calcium flux. Our results suggest that CCK may play a role in modulating the human mucosal immune system during digestion and thus, should be added to the list of the neuropeptides that affect the mucosal immune system.
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PMID:The inhibition effect of cholecystokinin in human colonic lamina propria lymphocyte proliferation, and reversal by the cholecystokinin receptor antagonist L-364718. 179 24

The effects of moderate cooling and of phenylarsine oxide on the contraction induced by two vasoactive peptides, angiotensin II (AII) and endothelin (ET-1), were investigated on endothelium-free rings of rat aortas. At 37 degrees C, the contraction induced by AII (0.1 microM) was transient. This decline in tension is unlikely to be due to rapid degradation of AII. In contrast, ET-1 (10 nM) induced a slowly developing and sustained contraction similar to the one observed with phorbol 12-13 dibutyrate (PDB, 22 nM). Moderate cooling (25 degrees C) significantly potentiated and prolonged the effect of AII but reduced the velocity of the ET-1 and PDB contraction, although the rate of the phenylephrine (1 microM) response remained unchanged. Phenylarsine oxide (100 microM) reduced the decline in tension in response to AII but inhibited the contraction elicited by ET-1 and PDB. In rings incubated in calcium-free medium (37 degrees C), AII induced a phasic contraction. This was followed by a second phasic contraction after calcium (2.5 mM) had been restored to the bath. The intensity of this second contraction decreased as the time between AII and calcium injection increased. This method, using regression analysis, permitted us to determine the time taken to reduce the contraction by half (4.8 min; r: 0.96), which may reflect the half-time of receptor sequestration. In calcium-free medium, the contractions induced by ET-1 and PDB were slow and sustained. Thus, rapid AII-receptor internalization leads to a short-term regulation of vascular tone whereas activation of protein kinase C by ET-1 may induce a long-term regulation.
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PMID:Different regulation of vascular tone by angiotensin II and endothelin-1 in rat aorta. 187 79

We used 3,4-diaminopyridine (3,4-DAP) and 4-aminopyridine (4-AP) as stimuli for evoking [3H]norepinephrine ([3H]NE) release in rabbit hippocampal slices to investigate the mechanism underlying the aminopyridines evoked [3H]NE release and the effect of protein kinase C activator phorbol ester PDB. 3,4-DAP and 4-AP evoked [3H]NE release were concentration dependent and enhanced by phorbol ester PDB. 4-AP (300 mumol.L-1) evoked [3H]NE release and enhancement of this evoked release by PDB were antagonized by protein kinase C inhibitor polymyxin B and almost abolished by tetrodotoxin. N-ethylmaleimide inhibited the facilitatory effect of PDB on 3,4-DAP evoked [3H]NE release implicating that G-protein is involved in the modulation of evoked [3H]NE release. 3,4-DAP evoked also dopamine release in caudate nucleus, and acetylcholine release in hippocampus suggesting that the mechanism by which 3,4-DAP evoked transmitters release is similar to that of electrical stimulation.
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PMID:[3,4-Diaminopyridine and 4-aminopyridine evoked neurotransmitter release]. 195 May 80


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