To understand the underlying mechanism of ethanol in tonic contraction, the effect of ethanol on phospholipase A2 and phospholipase C activities and the effects of phospholipase inhibitors on ethanol-induced contraction of cat gastric smooth muscle were tested. Circular muscle strips (2.0 × 0.2 cm) obtained from the fundus of cat stomach were used to measure isometric contraction. Ethanol elicited tonic contraction and activated phospholipase A2 activity in a dose-dependent manner. Phospholipase A2 inhibitors, manoalide (0.1-10 μM) and oleyloxyethyl phosphorylcholine (1-10 μM), significantly inhibited ethanol-induced contraction. Furthermore, 342 mM ethanol-induced contraction was significantly inhibited by cyclooxygenase inhibitors, ibuprofen (10-100 μM) and indomethacin (10-100 μM), but not by lipoxygenase inhibitors. On the other hand, phospholipase C inhibitors had no effect on ethanol-induced contraction, indicating that phospholipase C is not involved in ethanol-induced contraction. It is suggested from the above results that ethanol-induced contraction in cat gastric smooth muscle is, in part, mediated by phospholipase A2 and cyclooxygenase pathways.
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