Participation of protein kinase C in endothelin‐1‐induced contraction in rat aorta: studies with a new tool, calphostin C
Journal Articles
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
Calphostin C at 10−6m was shown to be selective and highly effective in inhibiting contractile responses of rat aortae to 12‐o‐tetradecanoylphorbol‐13‐acetate, while it had no effect on contractile responses to elevated KCl.In the rat aorta, endothelin‐1 (ET‐1) developed a sustained tonic contraction dose‐dependently in both normal Ca2+‐containing Krebs and Ca2+‐free Krebs containing 1 mm EGTA. Calphostin C (10−6m), a selective protein kinase C inhibitor, antagonized the maximal tensions for cumulative addition of 10−8m ET‐1 by 13.2% in Ca2+‐containing medium and 25.8% in Ca2+‐free Krebs containing 1 mm EGTA.In both Ca2+‐containing medium and Ca2+‐free Krebs containing 1 mm EGTA, precontraction with 10−8m ET‐1 had no effects on the contractile response to subsequently added 10−6m 12‐o‐tetradecanoylphorbol‐13‐acetate (TPA), an activator of protein kinase C.In Ca2+‐free Krebs containing 1 mm EGTA, precontraction with 10−6m TPA potentiated the contractile response to subsequently added 10−8m ET‐1, whereas this potentiation was abolished by pretreatment with 10−6m calphostin C. The mechanism of the TPA‐induced potentiating effect remains to be determined.These results suggest that the participation of protein kinase C in the 10−8m ET‐1‐induced contraction may be 13.2% and 25.8% in the presence and absence of extracellular Ca2+, respectively, and that mechanisms other than protein kinase C may be predominantly responsible for ET‐1‐induced tonic contraction.
