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 effects of substrate condition and ADP beta S on the pCa2+-tension relationships were investigated, using alpha-toxin permeabilized rabbit mesenteric artery at 37 degrees C. The contraction induced by 10 microM Ca2+ solution after permeabilization was as large as that induced by 145 mM K+ PSS solution containing 10 microM NE in the intact tissue, indicating that the majority of the cells were permeabilized. The Ca2+ sensitivity was greatly affected by the substrate condition and increasing the ratio of ATP/CP induced a leftward shift of the pCa2+-tension curve. Addition of 100 microM ADP beta S had a similar effect. When the ATP/CP ratio was high, the 0.1 microM Ca2+ solution relaxed the tissue precontracted by 10 microM Ca2+ solution more slowly showing hysteresis. One mM vanadate, which is reported to relax muscle by forming actomyosin-ADP-Vi (AM-ADP-Vi), completely inhibited both contractions induced by 0.18 microM Ca2+ solution containing 2 mM MgADP and 0.3 microM Ca2+ solution containing 0.3 microM PDBu. These results indicated that the population of AM-ADP complex in the crossbridge had increased due to the accumulation of ADP inside the tissue or activation of PKC and that the inhibition of ADP release from AM-ADP complex may be playing a key role in increasing Ca2+ sensitivity of myofilaments.
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PMID:Possible involvement of actomyosin ADP complex in regulation of Ca2+ sensitivity in alpha-toxin permeabilized smooth muscle. 259 Feb 38

The vascular effects of phorbol 12,13-dibutyrate (PDBu) were studied in the dog saphenous vein. PDBu (1 microM) caused contraction (0.58 +/- 0.22 g/mg wet wt.) and Ca uptake (74.2 +/- 41.2 mumol/kg wet wt.) which were unaffected by 10 microM phentolamine (N = 6). The PDBu-induced contraction was greatly (60-80%) inhibited in Ca2+-free solution. 45Ca efflux measurements performed in Ca2+-free solution showed that PDBu did not cause Ca release from intracellular storage sites. The contractile response to PDBu (1 nM-1 microM) was significantly correlated with the magnitude of Ca uptake; contraction and the rise in tissue Ca2+ also had a similar time course. Correlation between the two measures persisted when the responses to PDBu were augmented by co-administration with 20 mM KCl. However, no synergism occurred between the two agonists. Both the contraction and Ca uptake responses to PDBu were reduced by nifedipine and verapamil, each at 1 microM. In the Triton X-100 skinned saphenous vein, where the voltage-dependent Ca channel is not functional, 10 microM PDBu did not cause contractions in the presence of 0.1 microM Ca2+. Thus, contraction of the intact saphenous vein by PDBu characteristically exhibits great Ca dependence and PDBu seems to activate the voltage-dependent Ca channel, presumably through stimulation of protein kinase C; the ensuing Ca entry is primarily responsible for contraction. However, the mechanism responsible for the PDBu-induced contractions that are resistant to Ca2+-free PSS or Ca entry blockers remains to be defined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phorbol 12,13-dibutyrate, an activator of protein kinase C, stimulates both contraction and Ca2+ fluxes in dog saphenous vein. 318 41

The vasculature of rat isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution (GPSS). When 5-hydroxytryptamine (5HT, 1 x 10(-4) M), or the calcium ionophore A23187 (1 x 10(-4) M), or 12-deoxyphorbol 13-phenylacetate (DOPPA, 1 x 10(-6) M), or 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA, 1 x 10(-6) M) or thymeleatoxin (TMX, 1 x 10(-6) M) was added to the GPSS for 5 min there was a gradual rise in perfusion pressure, whereas resiniferatoxin (RFX, 1 x 10(-6) M) was without effect. Pre-treatment of the tissue with the protein kinase C (PKC) inhibitor Ro 31-8220 (1 x 10(-6) M) significantly reduced the rise in perfusion pressure in response to 5HT, DOPPA, DOPPAA and TMX, but not that to A23187. Platelet-activating factor (PAF, 5 x 10(-6) M) caused an almost immediate but transient rise in perfusion pressure, followed by a more gradual rise, neither response being blocked by Ro 31-8220. When blood vessels of the mesentery alone were perfused with gelatin-free PSS, PAF caused a transient rise in perfusion pressure, but with no subsequent gradual rise over 5 min. After Ca(2+)-depletion this transient response was also absent. In contrast, when blood vessels were perfused with gelatin-free PSS, DOPPA and TMX still caused gradual rises in perfusion pressure, which were totally abolished by Ro 31-8220. TMX had no effect at all when the tissue was depleted of Ca2+, whereas the response to DOPPA was only partially reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasoconstriction in rat isolated mesentery and small intestine in response to various activators of protein kinase C. 774 Oct 37

1. Mechanisms of Ca2+ sensitization of force production by noradrenaline were investigated by measuring contractile responses, intracellular Ca2+ concentration ([Ca2+]i) and phosphorylation of the myosin light chain (MLC) in intact and alpha-toxin-permeabilized rat mesenteric small arteries. 2. The effects of noradrenaline were investigated at constant membrane potential by comparing fully depolarized intact arteries in the absence and presence of noradrenaline. Contractile responses to K-PSS (125 mM K+) and NA-K-PSS (K-PSS + 10 microM noradrenaline) were titrated to 30 and 75%, respectively, of control force, by adjusting extracellular Ca2+ ([Ca2+]o). At both force levels, [Ca2+]i was substantially lower with NA-K-PSS than with K-PSS. With K-PSS, the proportion of MLC phosphorylated (approximately 30%) was similar at 30 and 75% of control force; with NA-K-PSS, MLC phosphorylation was greater at the higher force level (40 vs. 34%). 3. In alpha-toxin-permeabilized arteries, the force response to 1 microM Ca2+ was increased by 10 microM noradrenaline, and MLC phosphorylation was increased from 35 to 45%. The protein kinase C (PKC) inhibitor calphostin C (100 nM) abolished the noradrenaline-induced increase in MLC phosphorylation and contractile response, without affecting the contraction in response to Ca2+. Treatment with ATP gamma S in the presence of the MLC kinase inhibitor ML-9 increased the sensitivity to Ca2+ and abolished the response to noradrenaline. 4. The present results show that that in rat mesenteric small arteries noradrenaline-induced Ca2+ sensitization is associated with an increased proportion of phosphorylated MLC. The results are consistent with a decreased MLC phosphatase activity mediated through PKC. Furthermore, while MLC phosphorylation is a requirement for force production, the results show that other factors are also involved in force regulation.
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PMID:Mechanisms of Ca2+ sensitization of force production by noradrenaline in rat mesenteric small arteries. 970 5

The effect of the thromboxane A(2) analogue U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F(2)(alpha)) on sustained contraction in the mouse aorta was investigated. U46619 induced concentration-dependent (1 - 100 nM) increases in contraction. These contractile responses were enhanced significantly under high-glucose-physiological salt solution (HG-PSS) (2-fold greater than normal-PSS) conditions. This hyperactivation may be associated with aortic dysfunction in diabetes. However, the mechanisms remain unclear. HG-PSS enhanced U46619-induced accumulation of endogenous diacylglycerol (DG). Phospholipase C inhibitor (U73122) suppressed DG accumulation under normal conditions; however, suppression was not observed under high-glucose conditions. The HG-PSS-induced enhancement of contraction was inhibited by protein kinase C (PKC) inhibitor (calphostin C). This result indicated that accumulated DG might increase PKC activity, which then stimulates DG kinase activation as a feedback mechanism. DG kinase inhibition also suppressed HG-PSS-induced enhancement of contraction. Increased myo-inositol incorporation was detected under high-glucose conditions, indicating an acceleration of phosphatidylinositol (PI)-turnover. Moreover, rho kinase inhibitor (Y27632) suppressed U46619-induced contraction exclusively in normal-PSS. These findings indicated that HG-PSS treatment increases DG synthesis derived from incorporated glucose, PKC and DG kinase activation, and enhances the U46619-induced contraction via acceleration of PI-turnover. This series of responses may be involved in the dysfunction of aorta under high-glucose conditions occurring in association with diabetes.
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PMID:High-glucose enhances a thromboxane A2-induced aortic contraction mediated by an alteration of phosphatidylinositol turnover. 1289 Aug 93