Staurosporine, a protein kinase inhibitor, attenuates intracellular Ca(2+)-dependent contractions of strips of rabbit aorta.
The protein kinase inhibitor staurosporine was found to be a potent relaxant of rabbit aortic strips contracted by various agonists. This relaxing effect was slow, long-lasting and in a non-competitive fashion against various agonists. The effect of staurosporine on the KCl-induced contraction was not altered by atropine, propranolol, theophylline or indomethacin. Staurosporine (5-200 nM) inhibited the contractile responses to prostaglandin F2 alpha (3 microM), endothelin (0.1 microM), phenylephrine (3 microM) and KCl (30 mM), with ED50 values of 10.8 +/- 0.6, 24.6 +/- 8.7, 48.8 +/- 7.0, 54.0 +/- 12.7 nM, respectively. Even in Ca(2+)-free physiological salt solution, staurosporine potently antagonized the contractile responses elicited by 10 microM prostaglandin F2 alpha and 0.1 microM endothelin; in fact it was more effective than it was in normal Ca2+ solution: ED50 of 11.3 +/- 3.8 vs. 21.0 +/- 4.4 nM (P less than 0.02), and of 10.6 +/- 3.6 vs. 24.6 +/- 4.3 nM (P less than 0.01), respectively. Thus, staurosporine has an equipotent inhibitory action on intracellular and extracellular calcium-dependent contractions of aortic tissues.
Sasaki
Y
Y
Biochemical Research Laboratory, Asahi Chemical Industry, Co., Ltd., Miyazaki, Japan.
Seto
M
M
Komatsu
K
K
Omura
S
S
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011817:Rabbits; D019311:Staurosporine
D000470:Alkaloids; D016232:Endothelins; D015237:Dinoprost; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium