Contractile potentiation by endothelin-1 involves protein kinase C-δ activity in the porcine coronary artery

Abstract

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 (PKCα, PKCβ1, PKCδ and PKCζ) were identified in the porcine coronary artery. PKCα and PKCδ were mostly in the cytosol fraction, whereas PKCβ1 and PKCγ were almost equally distributed in the cytosol and membrane fractions in the resting and contractile states. Of the four isoforms, only PKCδ was translocated from the cytosol to the membrane fraction during the contractile potentiation by ET-1. These results suggest that the activity of PKCδ, a Ca2+-independent PKC isoform, is involved in the potentiation of 5-HT-induced contraction by ET-1 in the porcine coronary artery.