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 contraction of cat gastric smooth muscle in a dose-dependent manner. Vanadate-induced contraction was totally inhibited by 2 mM EGTA and 1.5 mM LaCl3 and significantly inhibited by 10 microM verapamil and 1 microM nifedipine, suggesting that vanadate-induced contraction is dependent on the extracellular Ca2+ concentration. and the influx of extracellular Ca2+ was mediated through voltage-dependent Ca2+ channel. Both protein kinase C inhibitor and tyrosine kinase inhibitor significantly inhibited the vanadate-induced contraction and the combined inhibitory effect of two protein kinase inhibitors was greater than that of each one. But calmodulin antagonists did not have any influence on the vanadate-induced contraction. On the other hand, both forskolin (1 microM) and sodium nitroprusside (1 microM) significantly inhibited vanadate-induced contraction. Therefore, these results suggest that both protein kinase C and tyrosine kinase are involved in the vanadate-induced contraction which required the influx of extracellular Ca2+ in cat gastric smooth muscle, and that the contractile mechanism of vanadate may be different from that of agonist binding to its specific receptor.
Sim
S S
SS
Department of Pathophysiology, College of Pharmacy, Chung-Ang University, Seoul, Korea.
Kim
C J
CJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002415:Cats; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D013270:Stomach / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D005576:Colforsin; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C