THE INVOLVEMENT OF PROTEIN-KINASE-C AND TYROSINE KINASE IN VANADATE-INDUCED CONTRACTION

Gastric smooth muscle of cats was used to investigate the involvement of protein kinase in vanadate-induced contraction. Vanadate caused a c ontraction of cat gastric smooth muscle in a dose-dependent manner. Va nadate-induced contraction was totally inhibited by 2 mM ECTA and 1.5 mM LaCl3 and significantly inhibited by 10 mu M verapamil and 1 mu M n ifedipine, suggesting that vanadate-induced contraction is dependent o n the extracellular Ca2+ concentration, and the influx of extracellula r Ca2+ was mediated through voltage-dependent Ca2+ channel. Both prote in kinase C inhibitor and tyrosine kinase inhibitor significantly inhi bited the vanadate-induced contraction and the combined inhibitory eff ect of two protein kinase inhibitors was greater than that of each one . But calmodulin antagonists did not have any influence on the vanadat e-induced contraction. On the other hand, both forskolin (1 mu M) and sodium nitroprusside (1 mu M) significantly inhibited vanadate-induced contraction. Therefore, these results suggest that both protein kinas e C and tyrosine kinase are involved in the vanadate-induced contracti on which required the influx of extracellular Ca2+ in cat gastric smoo th muscle, and that the contractile mechanism of vanadate may be diffe rent from that of agonist binding to its specific receptor.