Contribution of phospholipase C and protein kinase C but not endothelin-converting enzyme to contractile responses of ethanol

Aim: To evaluate the possible roles of phospholipase C, protein kinase C, and endothelin-converting enzyme on contractions induced by ethanol (164 mM) in isolated gastric fundal strips of mice. Materials and methods: After the mice were killed, the stomach of each was removed and longitudinal muscle strips were prepared from the gastric fundus. The strips were mounted in organ baths and their responses were recorded isometrically. Ethanol (164 mM) was added to the organ baths and a steady-state contraction was obtained. Aft er the fi rst ethanol response was recorded, the preparations were incubated separately with lidocaine (1-100 μM), neomycin (10-500 μM), safingol (0.5-5 μM), and SM-19712 (1-50 μM) for 40 min. The second ethanol response was then examined in the presence of the drug used in the incubation period. Results: Lidocaine (1-100 μM), a local anesthetic agent, did not modulate the contractions induced by ethanol in isolated gastric fundal strips of mice. In contrast, neomycin (10-500 μM), a selective inhibitor of phospholipase C, and safingol (0.5-5 μM), a selective inhibitor of protein kinase C, decreased the ethanol-induced contractions. SM-19712 (1-50 μM), a selective inhibitor of endothelin-converting enzyme, failed to affect these contractions. Conclusion: The contractile effect of ethanol may be muscular rather than neuronal in the gastric fundal strips of mice. In addition, phospholipase C and protein kinase C pathways may have a role in contractions due to ethanol in the mouse gastric fundus. On the other hand, endothelin-converting enzyme may not have a regulatory role in the contractile responses of ethanol in the same tissue.