Probable involvement of epsilon-isoform of protein kinase C in rat bronchial smooth muscle contraction induced by acetylcholine

Abstract

Although the role of protein kinase C (PKC) has been suggested in agonist-induced bronchial smooth muscle contraction, the PKC isoform(s) involved in this phenomenon is not clear now. In the present study, the effects of three PKC inhibitors, GF1092603X, Gö6976 and rottlerin on acetylcholine (ACh)-induced bronchial smooth muscle contraction were examined to identify the PKC isoform(s) involved in the contraction. Bronchial smooth muscles were pretreated with each PKC inhibitor (10(-6) and 10(-5) M) 30 min before cumulative administration of ACh. In another series of experiments, the effects of PKC inhibitors on the maximal contraction induced by 10(-3) M ACh were determined: the inhibitors were cumulatively administered (10(-8)- 10(-5) M) after the ACh-induced contraction reached plateau. The ACh-induced bronchial smooth muscle contraction was significantly inhibited by GF109203X (inhibitor of PKC alpha, beta, gamma, delta and epsilon) but not by Gö6976 (PKC delta, beta and gamma inhibitor) and rottlerin (PKC delta and theta inhibitor). Moreover, mRNA and protein of PKC epsilon were detected in rat bronchial smooth muscle. Taken together, PKC epsilon might be involved in the ACh-induced bronchial smooth muscle contraction in rats.