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)

1. The effects of leukotriene D4 (LTD4) on the mechanical properties of smooth muscle cells from the guinea-pig basilar artery were investigated in whole and chemically skinned muscle strips. 2. In strips with an intact endothelium, 5-hydroxytryptamine (5-HT; 10 microM), LTD4 and LTC4 (1 microM), STA2 (1 nM-10 nM) and high K+ (30 mM-128 mM) generated contractions. These comprised an initial phasic and subsequently generated tonic response with different amplitudes. Acetylcholine (ACh, 0.1-10 microM) inhibited and methylene blue (1-10 microM) enhanced the tonic component of these contractions in endothelium-intact muscle strips. In endothelium-denuded tissues, methylene blue had no effect on mechanical responses and ACh produced a further contraction in the presence of LTD4. 3. When the endothelium was removed, the amplitude of contractions induced by all tested stimulants markedly increased. In intact muscle strips, the order of potency for the production of a maximum response was; 128 mM K+ greater than STA2 greater than LTD4 = LTC4 = 5-HT. Following removal of the endothelium; STA2 greater than 128 mM K+ greater than LTD4 = LTC4 much greater than 5-HT. 4. In endothelium-denuded strips, the selective LTD4 antagonists, ONO-RS-411 and FPL 55712 inhibited the LTD4-induced contraction. In contrast, guanethidine, prazosin, yohimbine, atropine and mepyramine had no effect. Indomethacin and a thromboxane A2(TXA2) antagonist, ONO-3708 also had no effect on LTD4-induced contractions in endothelium-denuded strips. 5. In endothelium-denuded strips, nifedipine inhibited the tonic contraction induced by LTD4 but not the phasic component. In Ca2+-free solution containing 2 mM EGTA, LTD4 produced only the phasic contractions. 6. In saponin-treated chemically skinned muscle strips, LTD4 had no effect on either the pCa-tension relationship or on the release of Ca2+ from intracellular stores. However, inositol 1,4,5-triphosphate released Ca2+ from the stores and 1,2-diolein, an activator of protein kinase C, enhanced the contractions induced by 0.3 microM Ca2+. 7. It was concluded that LTD4 acts on both the endothelium and on the smooth muscle cells of the guinea-pig basilar artery. It stimulates the release of endothelium-derived relaxing factor (EDRF) which tends to inhibit the LTD4-induced contraction. It also interacts with receptors on the smooth muscle and produces a contraction as a result of an increase in both voltage-dependent and receptor-activated Ca2+ influx and, in part, the release of Ca2+ from cellular storage sites.
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PMID:Some effects of leukotriene D4 on the mechanical properties of the guinea-pig basilar artery. 325 45

Dihomogammalinolenic acid (2.5-20 microM) added to suspensions of washed human platelets induces platelet shape change and the formation of 1,2-diacylglycerol and phosphatidic acid, indicating the activation of phospholipase C. It also stimulates the phosphorylation of a 40 kDa protein, indicating the activation of protein kinase C. Dihomogammalinolenic acid is converted mainly to 12-hydroxyheptadecadienoic acid and to a smaller extent to prostaglandin E1 and thromboxane B1. Small quantities of the lipoxygenase product 12-hydroxyeicosatrienoic acid are also observed. Indomethacin, by blocking platelet cyclooxygenase, prevents the activation of phospholipase C, protein kinase C, and platelet shape change induced by dihomogammalinolenic acid. Compound UK 38485, a specific thromboxane synthetase inhibitor, does not block platelet activation induced by dihomogammalinolenic acid. The results indicate that endoperoxides derived from dihomogammalinolenic acid, such as prostaglandin G1 or prostaglandin H1, may be responsible for the stimulation of phospholipase C and protein kinase C, and for the induction of platelet shape change. Eicosapentaenoic acid does not activate platelets and is poorly metabolized by platelet cyclooxygenase and lipoxygenase. Eicosapentaenoic acid is a better inhibitor of platelet activation induced by various agonists in washed platelets than dihomogammalinolenic acid. Eicosapentaenoic acid and dihomogammalinolenic acid are, however, equally effective in inhibiting aggregation induced by collagen in platelet-rich plasma. We suggest that eicosapentaenoic acid might be a better antithrombotic agent than dihomogammalinolenic acid.
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PMID:Dihomogammalinolenic acid, but not eicosapentaenoic acid, activates washed human platelets. 608 12

The present study investigated the mechanisms involved in the mitogenic action of epidermal growth factor (EGF) in cultured human myometrial smooth muscle cells. The cells contained EGF/transforming growth factor-alpha (TGF-alpha) receptors as well as EGF and TGF-alpha mRNA transcripts and the corresponding proteins. Culturing with human EGF resulted in concentration- and time-dependent increases in cell density. The maximal increase was seen at 1 nM followed by a decrease to control levels at 100 nM EGF. The EGF increased cell density from 4 to 8 days followed by a plateau coinciding with the cells reaching confluence. EGF treatment concomitantly decreased the average size of cells. TGF-alpha mimicked EGF and there was no synergism between the two, suggesting a common mechanism of action. Although the presence of 10% fetal bovine serum enhanced overall cell growth, it was not required for EGF and TGF-alpha action. The receptor antibody, which is directed against the extracellular domain and can inhibit ligand binding to the receptors, dramatically inhibited the basal cell growth and exogenous EGF reversed the antibody effect. While TGF-alpha antibody was only marginally effective, EGF antibody had no effect on basal cell growth. Lavendustin (a tyrosine kinase inhibitor), calphostin (a protein kinase C inhibitor), but not H-89 (a protein kinase A inhibitor), inhibited EGF action. Indomethacin, a cyclo-oxygenase inhibitor, completely inhibited, whereas nordihydroguaiaretic acid, a lipoxygenase inhibitor, slightly inhibited EGF action. While estradiol-17 beta modestly inhibited basal as well as EGF-stimulated myometrial smooth muscle cell density, progesterone had no effect. In summary, mitogenic action of EGF in human myometrial smooth muscle cells does not require serum components and it involves tyrosine kinase and protein kinase C signaling and eicosanoids from the cyclooxygenase pathway of arachidonic acid metabolism.
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PMID:Analysis of epidermal growth factor action in human myometrial smooth muscle cells. 756 38

We present evidence for the presence of specific, high-affinity binding sites for tritiated phorbol 12,13-dibutyrate on osteosarcoma-derived (HT-3) cells. Activation of protein kinase C by a phorbol ester resulted in an inhibition of alkaline phosphatase activity and the accumulation of prostaglandin E2. Indomethacin blocked prostaglandin E2 production and enhanced alkaline phosphatase activity. These data suggest that prostaglandin E2 is enhanced by activation of protein kinase C, and in turn, alkaline phosphatase activity is reduced.
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PMID:Activation of protein kinase C and the involvement of prostaglandin E2 in the inhibition of osteosarcoma-derived cell alkaline phosphatase activity. 766 74

The vasculature of the isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution in vitro. Various phorbol-related compounds that are known to have different affinities for the protein kinase C (PKC) isoenzymes, and bradykinin (BK), were tested for their ability to cause the microvascular endothelium to become permeable to injected colloidal carbon (CC). Phorbol 12,13-dibutyrate (PDB), 12-deoxyphorbol 13-phenylacetate (DOPPA), thymeleatoxin (TMX), and resiniferatoxin (RFX), each at a concentration of 1 microM, were found to increase permeability. Pretreatment with the PKC inhibitor Ro 31-8220 (1 microM) significantly reduced the response to all of these compounds. Indomethacin (1 microM), on the other hand, reduced only the effect of RFX. 12-Deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA) (1 microM) and BK (10 microM) did not increase CC leakage. These results suggest that the Ca(2+)-dependent PKC alpha-isoenzyme was involved in the increase in endothelial permeability. BK does not appear to stimulate PKC activity in this experimental situation.
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PMID:Stimulation of protein kinase C activity may increase microvascular permeability to colloidal carbon via alpha-isoenzyme. 784 93

We have shown that acetylcholine (ACh)-induced contraction of esophageal circular muscle cells is mediated by activation of protein kinase C (PKC). We now examine the role of phospholipase A2 (PLA2). ACh increases [3H]arachidonic acid release in esophageal but not in lower esophageal sphincter (LES) muscle. In addition, ACh-induced contraction of esophageal but not of LES cells was reduced by the PLA2 antagonist dimethyleicosadienoic acid and by antiserum to a 100-kDa cytosolic PLA2 (cPLA2). These data suggest that the 100-kDa cPLA2 plays a role in ACh-induced contraction of esophageal but not of LES muscle. In esophageal cells, arachidonic acid produced by PLA2 caused little contraction by itself but potentiated contraction induced by the PKC agonist diacylglycerol (DAG). The free fatty acids linoleic acid and linolenic acid also potentiated DAG-induced contraction. Indomethacin and nordihydroguaiaretic acid had no effect on arachidonic acid-induced potentiation of DAG. The potentiation of DAG-induced contraction by arachidonic acid was inhibited by the PKC inhibitor H-7, but it was not affected by the calmodulin inhibitor CGS-9343B. We conclude that a 100-kDa cPLA2 participates in ACh-induced esophageal contraction by producing arachidonic acid and potentiating DAG-induced activation of a PKC-dependent pathway.
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PMID:Role of 100-kDa cytosolic PLA2 in ACh-induced contraction of cat esophageal circular muscle. 794 41

Our previous study provided a novel assay system utilizing devitalized bone slices for study of the differentiation of osteoclast progenitors into preosteoclasts and mature osteoclasts among calvarial cells of mouse embryos. Using this assay system, we examined the effect of phorbol myristate acetate (PMA) on osteoclast formation as assessed by the appearance of tartrate-resistant acid phosphatase (TRAP)-positive cells and bone resorption lacunae. PMA alone was directly unable to induce the appearance of TRAP-positive cells and bone resorption lacunae of calvarial bone cells of mouse embryos. However, PMA markedly stimulated increases in the number of TRAP-positive cells and area of the resorption lacunae of the calvarial cells when the bone cells were primed by 1 alpha,25-(OH)2D3. This stimulatory effect of PMA was dose dependent. H-7, having relatively high affinity for protein kinase C, strongly inhibited in a dose-dependent fashion the stimulatory effect of PMA on the bone resorption of the hormone-primed calvarial cells. We also examined the involvement of prostaglandin in this stimulatory effect of PMA. Indomethacin, a cyclooxygenase inhibitor, markedly abolished the stimulatory effect of PMA on the bone resorption of the calvarial cells. PMA stimulated prostaglandin E2 (PGE2) production by the calvarial cells primed with 1 alpha,25-(OH)2D3 in a dose-dependent fashion. However, the PMA stimulation of the PGE2 production was significantly inhibited by H-7 and also by indomethacin. Furthermore, we observed that the addition of PGE2 to the calvarial cells primed with 1 alpha,25-(OH)2D3 for 1 or 3 days resulted in an increased number of TRAP-positive cells and increased bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phorbol myristate acetate stimulates osteoclast formation in 1 alpha,25-dihydroxyvitamin D3-primed mouse embryonic calvarial cells by a prostaglandin-dependent mechanism. 803 Apr 34

The effect of endothelin-1 (ET-1) on the proximal tubule remains unclear. This may be due to a biphasic effect on transport in this segment. We hypothesized that ET-1 has a biphasic effect on fluid absorption (Jv) in the proximal straight tubule and that its inhibitory effect is superimposed on its stimulatory effect. ET-1 (10(-13) M) stimulated Jv from 0.68 +/- 0.07 to 1.11 +/- 0.20 nl/mm/min, a 60% increase (P < 0.04). 10(-12) and 10(-10) M ET-1 had no significant effect. 10(-9) M ET-1 reduced Jv from 0.81 +/- 0.19 to 0.44 +/- 0.15 nl/mm/min (P < 0.009). Staurosporine (STP, 10(-8) M) prevented both 10(-9) and 10(-13) M ET-1 from altering Jv significantly indicating that protein kinase C (PKC) is involved. Indomethacin (10(-5) M) blocked the inhibition produced by 10(-9) M ET-1. ETI (10(-6) M), a lipoxygenase inhibitor, also blocked ET-1 inhibition of Jv. Interestingly ET-1 (10(-9) M) stimulated Jv in the presence of both indomethacin and ETI. When 10(-9) M ET-1 was added in the presence of 10(-5) M quinacrine, a phospholipase (PL) inhibitor, Jv also increased from 1.02 +/- 0.20 to 1.23 +/- 0.22 nl/mm/min (P < 0.03). STP blocked this increase. We conclude that (a) 10(-13) M ET-1 stimulates fluid absorption by activating PKC; (b) 10(-9) M ET-1 decreases Jv by PKC-, PL-, cyclooxygenase-, and lipoxygenase-dependent mechanisms; and (c) the inhibitory effect of ET-1 on Jv is superimposed on the stimulatory effect.
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PMID:Endothelin's biphasic effect on fluid absorption in the proximal straight tubule and its inhibitory cascade. 820 Sep 94

To determine the role of protein kinase C (PKC) in airway submucosal gland secretion, we examined the effect of a selective PKC stimulant, phorbol 12-myristate 13-acetate (PMA), on mucus glycoprotein (MGP) secretion, fluid secretion and intracellular Ca2+ concentration ([Ca2+]i) in isolated feline submucosal glands. MGP and fluid secretions were estimated by measuring trichloroacetic acid (TCA)-precipitable glycoconjugates and 22Na-efflux, respectively, from isolated glands. [Ca2+]i was measured using a Ca(2+)-sensitive fluorescent dye, Fura 2. PMA itself produced a significant increase in MGP secretion in a dose-dependent fashion (173% of control at 10(-5) M). PMA also produced a significant increase in 22Na-efflux (151% of baseline rate constant at 10(-5) M). Indomethacin failed to alter the increase in MGP secretion or in 22Na-efflux in response to PMA. Two PKC inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and sphingosine, inhibited both MGP secretion and 22Na-efflux stimulated by PMA; there was only a partial inhibition after stimulation by methacholine (MCh). PMA did not significantly alter [Ca2+]i and H-7 did not alter the MCh-induced [Ca2+]i rise. These findings indicate that PKC has a direct stimulatory role in stimulus-secretion coupling of airway submucosal gland secretion.
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PMID:A stimulatory role of protein kinase C in feline tracheal submucosal gland secretion. 821 Jul 61

Gram-negative sepsis/septic shock in the newborn continues to be a major medical problem, causing high mortality. Hyperglycemia followed by hypoglycemia is a common symptom in endotoxic shock. However, the mechanism of newborn glucoregulatory response to endotoxin has not been well understood. Paradoxically, monocyte-phagocytes can contribute to shock by overwhelming secretion of cytokines and also host defense by detoxifying endotoxin. Since monocyte-phagocyte function is immature in the newborn, this study was performed to evaluate Kupffer cell's role in liver glycogenolysis during endotoxic shock. Endotoxin (LPS) induced hyperglycemia in 10-day-old rats, and increased net glucose output in the isolated perfused liver. 1) Cytarabine decreased Kupffer cell function (decreased hepatic colloid carbon uptake) and blunted LPS-increased liver net glucose output in the Cytarabine + LPS-treated group (104 +/- 4 vs. 146 +/- 3 micrograms/min/g wet liver in the LPS-treated group: P < .001). 2) Indomethacin (IND) suppressed LPS-induced liver net glucose output in the LPS + IND-treated group (133 +/- 5 vs. 146 +/- 3 micrograms/min/g wet liver, P < .05). Thus, prostaglandins were suggested to contribute to glycogenolysis in the 10-day-old rat liver. 3) Phorbol 12-myristate 13-acetate (PMA) increased liver net glucose output (166 +/- 4 micrograms/min/g wet liver), and H-7, a protein kinase C inhibitor, blunted PMA-induced liver glucose output (140 +/- 2 micrograms/min/g wet liver, P < .05). H-7 enhanced LPS-induced liver net glucose output (196 +/- 9 micrograms/min/g wet liver, P < .01). Therefore, protein kinase C may not be the dominant cell signaling system for LPS stimulation in suckling rat Kupffer cells.
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PMID:Lipopolysaccharide alters suckling rat liver glycogenolysis. 832 90


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