Effects of Protein Kinase C Inhibitors on Ethanol-Induced Contractions in Isolated Rat Aorta

Abstract

The activation of intracellular contractile proteins induces vascular contraction mediated through signal transduction mechanisms. Protein kinase C (PKC) is involved in this signal transduction. The purpose of the present study was designed to investigate the role of PKC on EtOH-, KCl- and phorbol 12, 13-dibutyrate (PDBu)-induced contractions in isolated rat aorta through the use of several different PKC inhibitors. Prior exposure to staurosporine inhibited both EtOH- and KCl-induced contractions in a concentration-dependent manner. The EtOH-induced contractions were completely inhibited by staurosporine (5 × 10−6 M) but complete inhibition of KCl-induced contractions was not observed. Staurosporine (10−7 M) also significantly inhibited the contractile response to single doses of both EtOH and PDBu. Bisindolylmaleimide (10−6 M) effectively inhibited contractile responses to both EtOH- and KCl, added cumulatively, and single doses of PDBu. Chelerythrine (10−7 M) inhibited maximal EtOH-induced contractions. These results suggest that PKC activation plays an important role in the mechanism(s) involved in the contractile activation of rat aorta smooth muscle by EtOH, KCl and PDBu. However, further work is required to elucidate the precise molecular mechanism.