Contractile potentiation by endothelin-1 involves protein kinase C-delta activity in the porcine coronary artery.
The relationship between potentiation of serotonin (5-hydroxytryptamine, 5-HT)-induced contraction by endothelin-1 (ET-1) and the activity of protein kinase C (PKC) was examined in the porcine coronary artery. Low concentrations (30-100 pM) of ET-1 selectively potentiated the 5-HT-induced contraction 1.5 to 2 times over the control without any additional increase in myosin light-chain phosphorylation. The potentiation was attenuated by PKC down-regulation caused by phorbol 12-myristate 13-acetate. By Western blot analysis with isoform-specific antibodies to PKC, at least four isoforms (PKCalpha, PKCbeta1, PKCdelta and PKCzeta) were identified in the porcine coronary artery. PKCalpha and PKCdelta were mostly in the cytosol fraction, whereas PKCbeta1 and PKCzeta were almost equally distributed in the cytosol and membrane fractions in the resting and contractile states. Of the four isoforms, only PKCdelta was translocated from the cytosol to the membrane fraction during the contractile potentiation by ET-1. These results suggest that the activity of PKCdelta, a Ca2+-independent PKC isoform, is involved in the potentiation of 5-HT-induced contraction by ET-1 in the porcine coronary artery.
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
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Obara
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Hata
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Sato
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Koide
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Ishii
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K
Nakayama
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D019332:Endothelin-1 / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007527:Isoenzymes / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D051745:Protein Kinase C-delta; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D013552:Swine
D019332:Endothelin-1; D016166:Free Radical Scavengers; D007527:Isoenzymes; D012701:Serotonin; D011493:Protein Kinase C; D051745:Protein Kinase C-delta