EC:2.7.11.13 - FACTA Search

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)

1. 5-Hydroxytryptamine (5-HT) produced a concentration-dependent increase in the membrane concentration of 1,2-diacylglycerol (DG) in the rabbit isolated basilar artery, but did not stimulate the hydrolysis of membrane phosphoinositide. 2. The 5-HT-induced accumulation of DG could be blocked with the putative phospholipase C inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC; 70 microM), but not with the protein kinase C inhibitor, 1-(5-isoquinolinesulphonyl)-2-methyl piperazine (H7; 50 microM). 3. Direct stimulation of protein kinase C with phorbol 12,13-dibutyrate (PDBu) produced sustained smooth muscle contraction which was fairly rapid in onset and could be reversed by H7 but not by NCDC. The inactive phorbol, 4 alpha phorbol 12,13-dideceonate, did not produce contraction in the basilar artery. 4. 5-HT-induced contractions (1 nM-100 microM) were blocked or greatly reduced in the presence of the protein kinase inhibitor H7 or polymyxin B, and with the phospholipase C inhibitor, NCDC. The concentrations of these inhibitors which abolished contraction to 5-HT, did not alter smooth muscle contraction produced in response to 30 mM K(+)-physiological salt solution (PSS). 5. These data suggest that DG production and the subsequent activation of PKC forms an important component of the cerebrovascular contractile response to 5-HT. As the DG does not appear to arise from membrane phosphatidylinositol, it appears that 5-HT can stimulate the production of this second messenger in cerebral arteries by a mechanism which is different from peripheral arteries.
...
PMID:5-hydroxytryptamine-stimulated accumulation of 1,2-diacylglycerol in the rabbit basilar artery: a role for protein kinase C in smooth muscle contraction. 201 23

X-irradiation and the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) act in a synergistic manner to increase the yield of transformed C3H10T1/2 cells in vitro. TPA modulated both translocation from the cytosol to the plasma membrane, and down regulation of protein kinase C (PKC) after prolonged (48 h) TPA exposure. N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), antipain, and soybean-derived Bowman-Birk inhibitor, protease inhibitors that suppress transformation of C3H10T1/2 cells, had no effect on these TPA-mediated alterations of PKC activity, suggesting that protease inhibitors suppress TPA-stimulated promotion in vitro via a PKC-independent pathway. Several experiments were performed to determine whether non-toxic concentrations of the PKC inhibitors, N-p-tosyl-L-lysine chloromethyl ketone (TLCK), TPCK, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), or 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine (H-7), modulated the movement of cells from a quiescent state into the cell cycle. TPCK and the combination of H-7 and W-7 lowered DNA synthesis when cells were stimulated to divide by TPA. Because other protease inhibitors that slow transformation in vitro did not have the same suppressive effect on DNA synthesis, the inhibitory pathway that suppresses carcinogenic activity is likely to be different from the suppression of DNA synthesis.
...
PMID:Suppression of phorbol ester-enhanced radiation-induced malignancy in vitro by protease inhibitors is independent of protein kinase C. 201 16

The mucosal-to-serosal and serosal-to-mucosal fluxes of Na+ and Cl- were measured in control mice and mice treated with heat-stable (ST) and heat-labile (LT) enterotoxins in the presence or absence of: Ca2(+)-ionophore A23187, an activator of Ca2(+)-calmodulin; or phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C(PKC); or 1-(5-isoquinolinyl sulphonyl)-2-methyl piperazine (H-7), an inhibitor of PKC. There was net secretion of Na+ and CL- in both experimental groups in contrast to net absorption in the control group. The addition of ionophore or PMA or ionophore + PMA resulted in net secretion of Na+ and Cl- in the control group and the effect of ionophore and pMA was found to be additive. The addition of ionophore did not cause any change in electrolyte fluxes in the ST toxin treated group, however, it increased the net secretion of Na+ and Cl- in the LT toxin treated group. PMA increased the net secretion of Na+ and Cl- in the St toxin treated group, however, it did not cause any change in Na+ and Cl- fluxes in the LT toxin treated group. H-7 did not reverse the effect of ST toxin, however, it reversed the effect of LT toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Differences between the mechanisms of action of heat-stable and heat-labile enterotoxins of Escherichia coli. 210 96

A role for protein kinase C (PKC) in mediation of prostaglandin E2 synthesis in human amnion cells has been suggested. We have investigated the specificity of the stimulation of PGE2 synthesis by phorbol esters and employed putative PKC inhibitors to demonstrate the specificity of PKC stimulation. The three phorbol esters, tetradecanoyl phorbol-13-acetate, phorbol-12,13-dibutyrate and phorbol-12,13-didecanoate gave concentration-dependent (10(-10)-10(-7)M) increases in PGE2 synthesis when added to amnion cells in monolayer, however, no effect was seen with the structurally similar phorbols phorbol-12-13-diacetate, 4 alpha phorbol-12-13-didecanoate or phorbol base. The stimulatory effect of TPA (10(-8)M) on amnion PGE2 synthesis could be prevented by coincubation with the putative protein kinase C inhibitors 1-(5-isoquinoline sulphonyl) piperazine, 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine, sphingosine and chlopromazine at concentrations of 10(-6)-10(-4)M. Addition of the transcription inhibitor actinomycin D at 10(-6)-10(-5)M prevented TPA (10(-8)M)-induced PGE2 synthesis. However, paradoxically, a further increase in PGE2 synthesis was seen when 10(-9)-10(-7)M actinomycin D was added together with TPA. The phospholipase A2 inhibitor quinacrine was able to prevent the TPA-induced increase in PGE2 synthesis even in the presence of exogenous arachidonic acid suggesting that phospholipase A2 may be a target for PKC action.
...
PMID:Regulation of prostaglandin E2 synthesis in human amnion by protein kinase C. 211 70

The acute incubation of mouse bone marrow-derived mast cells with low concentrations of agents known to activate protein kinase C [phorbol myristate acetate (PMA), 1,2-dioctanoyl-sn-glycerol (diC8), and 1-oleoyl-2-acetyl-glycerol (OAG)] caused an enhancement of beta-hexosaminidase release stimulated by the calcium ionophore A23187. Higher concentrations of protein kinase C activators tended to inhibit A23187- or antigen-induced preformed mediator release. All concentrations studied induced a striking mast cell hyporesponsiveness to the mediator release augmenting effect of adenosine. Agents that have been reported to block protein kinase C activity [1-(5-isoquinolinesulfonyl)-2-methyl-piperazine dihydrochloride (H-7) and sphingosine] demonstrated diverse responses in this system. Up to 100 microM H-7 failed to affect mast cell beta-hexosaminidase release in the presence or absence of PMA and secretagogue. Sphingosine (10 microM) was a potent inhibitor of antigen- or A23187-induced mediator release as well as adenosine responsiveness. Sphingosine also blocked the effects of PMA noted above in a dose-dependent fashion. The generation of leukotriene C4 (LTC4) by stimulated mast cells surprisingly was not affected by concentrations of diC8 that significantly inhibited granule-associated mediator release. Translocation of protein kinase C activity from the cytosol to the mast cell membrane was evident in cells briefly pretreated with A23187, adenosine alone, and diC8 in the presence of Tyrode's buffer, A23187, or adenosine. These findings lend further support to the contention that signal transduction from mast cell adenosine receptors to processes that regulate degranulation may involve protein kinase C.
...
PMID:Modulation of mast cell responses to adenosine by agents that alter protein kinase C activity. 214 Dec 57

The tumor-promoting phorbol ester 4 beta-phorbol 12-myristate 13-acetate (PMA) inhibited thrombin-stimulated arachidonic acid (AA) release in rabbit and human platelets. PMA was effective over the same concentration range that activates protein kinase C in intact rabbit platelets: IC50 vs thrombin = 0.5 nM, greater than 90% inhibition at 10 nM. Suppression of thrombin-stimulated AA release was evident within 5 min of pretreatment with 1 nM PMA. A non-tumor-promoting phorbol ester, 4-O-methyl PMA, showed a very weak ability to inhibit AA release. Thrombin-stimulated serotonin secretion was progressively inhibited by PMA pretreatment in platelets, while PMA was a stimulus for secretion at higher concentrations. 1-(5-Isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), a selective inhibitor of protein kinase C, blocked PMA-induced inhibition of AA release. Furthermore, H-7 enhanced the effect of thrombin on AA release. PMA pretreatment reduced the inhibitory effect of thrombin on forskolin-stimulated cAMP accumulation, but had no effect on nonstimulated cAMP metabolism in the presence of thrombin. PMA did not inhibit AA release caused by A23187 or melittin. In digitonin-permeabilized platelets, thrombin plus guanosine 5'-(3-O-thio)triphosphate (GTP gamma S)-stimulated AA release, but not GTP gamma S- and AIF4(-)-stimulated AA release, was abolished by PMA pretreatment. These results suggest that activation of protein kinase C may exert negative feedback on the receptor-mediated activation of phospholipase A2. A possible uncoupling of thrombin receptor to GTP-binding protein leading to activation of phospholipase A2 by PMA pretreatment is discussed.
...
PMID:Modes of inhibitory action of 4 beta-phorbol 12-myristate 13-acetate in thrombin-stimulated arachidonic acid release in intact and permeabilized platelets. 215 60

We investigated the effect of dioctanoylglycerol (DOG), a second messenger of protein kinase C (PKC) activation, in the absence and presence of neutrophils in isolated perfused guinea pig lung. DOG was given after a base-line isogravimetric steady-state period. Pulmonary capillary pressure (Ppc) and change in lung weight (delta W) were monitored at 15, 30, and 60 min. Capillary filtration coefficient (Kf,c, an index of vascular permeability) was measured during base-line period and at 30 min. DOG increased the Ppc and delta W at 30 and 60 min, and the Kfc at 30 min. Monooctanoylglycerol, a monoacylglycerol that does not activate PKC, had no effect on Ppc, Kf,c, and delta W. Pretreatment with two different PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine or staurosporin, prevented the pulmonary response to DOG. With neutrophils present, DOG caused greater increases in delta W and the (wet-dry)-to-dry wt ratio compared with DOG group. Response to DOG+ neutrophils was due to oxygen radical production because it was prevented by pretreatment with catalase and because DOG increased superoxide release from neutrophils. PKC activation using DOG in the isolated lung results in pulmonary edema mediated by increases in capillary pressure and vascular permeability. Lung weight-gain response to DOG is greater in the presence of neutrophils. Response to DOG+ neutrophils is mediated by oxygen radicals.
...
PMID:Mechanisms of pulmonary edema induced by a diacylglycerol second messenger. 215 34

We studied the effect of a potent inhibitor of protein kinase C, polymyxin B (PMXB), on superoxide anion (O2-) release by human polymorphonuclear leukocytes (PMNL). PMXB was compared with another inhibitor of protein kinase C, 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine (H-7). Both PMXB and H-7 inhibited phorbol myristate acetate (PMA)-stimulated O2- release. Formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated O2- release by cytochalasin B-treated PMNL was not inhibited significantly by either PMXB or H-7. 1-Oleoyl-2-acetyl-glycerol (OAG,25-100 microM) stimulated PMNL to release O2- with a long lag-time (8-10 min). Although H-7 inhibited OAG-stimulated O2- release, PMXB augmented the OAG-stimulated response by increasing rate and reducing lag time. The augmenting effect of PMXB was evident only when added after stimulation by OAG, with maximum effect observed at 3 min after addition of OAG. The augmenting effect was also seen with PMXB immobilized on agarose beads. PMXB did not affect the respiratory burst response to 1,2-dioctanoylglycerol. PMXB-augmented, OAG-stimulated O2- release was inhibited by the addition of H-7 before OAG. In contrast to the effect on O2- release, OAG-stimulated protein phosphorylation was inhibited similarly by either PMXB or H-7, when these agents were added 3 min after stimulation by OAG. These results suggested that initial activation of protein kinase C by OAG is essential for O2- release, but that PMXB acts in a manner independent from protein kinase C to augment OAG-stimulated O2- release. When priming by OAG for enhanced O2- release (as opposed to direct stimulation of O2- release) in FMLP-stimulated PMNL was examined, PMXB inhibited O2- release in OAG-primed PMNL, suggesting that protein kinase C is involved in priming of PMNL by OAG.
...
PMID:Effects of polymyxin B on superoxide anion release and priming in human polymorphonuclear leukocytes. 215 77

Insulin (63 microM) stimulated endogenous dopamine (DA) release from tuberoinfundibular neurons. This effect was independent on the presence of extracellular glucose and did not involve the outward transport of DA, mediated by its membrane carrier. By contrast this effect was completely prevented by the removal of extracellular Ca++ ions in presence of the Ca(++)-chelator ethyleneglycol-2-(2-aminoethyl)-tetracetic acid (EGTA). Furthermore 1-(5-isoquinolinyl-sulfonyl)-2-methyl-piperazine (H7), a compound which behaves as a putative inhibitor of protein kinase C (PK-C) (10 microM), completely counteracted the stimulation of endogenous DA release induced by insulin. Amiloride (300 microM) and its 5-amino nitrogen atom-substituted derivative, 5-(N-methyl-N-(guanidinocarbonylmethyl) amiloride (MGCMA) (10 microM), a highly selective inhibitor of the Na(+)-H+ membrane antiporter, were both able to prevent the stimulatory action exerted by insulin on endogenous DA release. Collectively, these results suggest that the transductional events by which insulin stimulated endogenous DA release from TIDA neurons may involve the activation of PK-C, the enhancement of Ca++ influx and the stimulation of the Na(+)-H+ exchange system.
...
PMID:Possible involvement of Ca++ ions, protein kinase C and Na(+)-H+ antiporter in insulin-induced endogenous dopamine release from tuberoinfundibular neurons. 215 21

1. Phorbol esters are known to inhibit phospholipase C-mediated hydrolysis of membrane phosphoinositide. This inhibition is attributed to participation of protein kinase C (PKC) in a negative-feedback control of phosphoinositide metabolism. We have tested this hypothesis by using different types of activators and inhibitors of PKC. 2. Phorbol-12,13-dibutyrate (PDB) inhibited the stimulatory effect of acetylcholine (ACh) on [3H]inositol monophosphate ([3H]IP) formation in cultured sympathetic neurons of the chick embryo and adrenal medulla of the rat. 3. Acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) activated neuronal PKC by 3- to 8-fold. The extent of PKC activation by 100 microM-ACh was comparable to that of 100 nM-PDB. Activation of PKC by pre-incubation of sympathetic neurons with ACh (or 5-HT) did not inhibit the stimulatory effects of ACh (or 5-HT) on [3H]IP formation. 4. Pre-treatment of sympathetic neurons or adrenal medulla with a PKC inhibitor H7 (1-(5-isoquinolinyl-sulphonyl)-2-methyl-piperazine) almost completely blocked activation of the enzyme induced by PDB, ACh or 5-HT. However, blockade of PKC did not prevent the inhibitory effects of PDB on ACh-induced [3H]IP formation. 5. Vasoactive intestinal polypeptide (VIP) and muscarine induced catecholamine secretion from the perfused adrenal medulla via formation of inositol-1,4,5-tirisphosphate (IP3). Phorbol-12,13-dibutyrate decreased muscarine-induced catecholamine secretion. However, activation of PKC by VIP had no effect on muscarine-induced catecholamine secretion and vice versa. 6. These results suggest that PKC is not negatively coupled to phosphoinositide hydrolysis in sympathetic neurons and chromaffin cells. Phorbol esters must have targets other than PKC to interfere with the phosphoinositide hydrolysis.
...
PMID:Phosphoinositide hydrolysis is not negatively regulated by protein kinase C in the peripheral tissues of rat and chick. 217 Jun 29

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>