Regulation of the Contraction Induced by Emptying of Intracellular Ca<SUP>2&#8290;</SUP> Stores in Cat Gastric Smooth Muscle

Regulation of the Contraction Induced by Emptying of Intracellular Ca<SUP>2&#8290;</SUP> Stores in Cat Gastric Smooth Muscle

<P> To investigate the mechanism of smooth muscle contraction induced by emptying of intracellular Ca<SUP>2&#8290;</SUP> stores, we measured isometric contraction and <SUP>45</SUP>Ca<SUP>2&#8290;</SUP> influx. CaCl<SUB>2</SUB> increased Ca<SUP>2&#8290;</SUP> store emptying- induced contraction in dose-dependent manner, but phospholipase C activity was not affected by the Ca<SUP>2&#8290; </SUP>store emptying-induced contraction. The contraction was inhibited by voltage-dependent Ca<SUP>2&#8290;</SUP> channel antagonists dose dependently, but not by TMB-8 (intracellular Ca<SUP>2&#8290;</SUP> release blocker). Both PKC inhibitors (H-7 and staurosporine) and tyrosine kinase inhibitors (genistein and methyl 2,5-dihydroxycinnamic acid) significantly inhibited the contraction, but calmodulin antagonists (W-7 and trifluoperazine) had no inhibitory effect on the contraction. The combined inhibitory effects of protein kinase inhibitors, H-7 and genistein, together with verapamil were greater than that of each one alone. In Ca<SUP>2&#8290;</SUP> store-emptied condition, <SUP>45</SUP>Ca<SUP>2&#8290;</SUP> influx was significantly inhibited by verapamil, H-7 or genistein but not by trifluoperazine. However combined inhibitory effects of protein kinase inhibitors, H-7 and genistein, together with verapamil were not observed. Therefore, this kinase pathway may modulate the sensitivity of contractile protein. These results suggest that contraction induced by emptying of intracellular Ca<SUP>2&#8290;</SUP> stores was mediated by influx of extracellular Ca<SUP>2&#8290;</SUP> through voltage-dependent Ca<SUP>2&#8290;</SUP> channel, also protein kinase C and/or tyrosine kinase pathway modulates the Ca<SUP>2&#8290;</SUP> sensitivity of contractile protein.