Asano M, Matsunaga K, Miura M, Ito K M, Seto M, Sakurada K, Nagumo H, Sasaki Y, Ito K
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
Eur J Pharmacol. 1995 Dec 29;294(2-3):693-701. doi: 10.1016/0014-2999(95)00616-8.
We examined the effects of staurosporine, a protein kinase inhibitor, on Ca2+ movements and contractions due to KCl and 12-deoxyphorbol 13-isobutyrate (DPB), which are thought to activate myosin light chain kinase and protein kinase C, respectively. In rabbit aortae, staurosporine inhibited contractions due to KCl (65.4 mM) and DPB (1 mu M) with IC50 values of 140.5 +/- 1.3 nM and 13.3 +/- 1.3 nM, respectively. Calphostin C, a putative inhibitor of protein kinase C, inhibited DPB-induced contraction with much less effect on the KCl-induced one. On the other hand, wortmannin, an inhibitor of myosin light chain kinase, was 4 times more potent on KCl-induced contraction than the DPB-induced one. Staurosporine at 100 nM decreased the rise in cytosolic Ca2+ due to KCl, whereas wortmannin did not affect it. In rabbit cerebral arteries permeabilized with beta-escin, staurosporine at 100 nM, but not 30 nM, inhibited Ca2+ -induced contraction in the presence of 1 mM ATP. The results indicate that staurosporine preferentially inhibits a contraction dependent on protein kinase C than that dependent on myosin light chain kinase in vascular smooth muscles. Its ability to inhibit KCl-induced contraction involves inhibition of voltage-dependent Ca2+ channels.
