Ethanol-induced relaxation of mouse esophagus: subcellular mechanisms

Ethanol (164 mm) produced reproducible relaxations in isolated mouse esophageal strips. Hexamethonium (10–500 μm), a ganglionic blocking agent, and lidocaine (10–100 μm), a local anesthetic agent, failed to affect the relaxations induced by ethanol in the mouse esophagus. Although verapamil (10–500 μm), a selective blocker of L‐type Ca2+ channels, failed to affect the relaxations to ethanol, ruthenium red (10–100 μm), a selective blocker of ryanodine receptors (intracellular Ca2+ channels), and cyclopiazonic acid (1–10 μm), a selective blocker of sarcoplasmic reticulum Ca2+ ATPase (SERCA), significantly inhibited these relaxations. In addition, tetraethylammonium (10–100 μm), a potassium‐selective ion channel blocker and Nω‐nitro‐l‐arginine (l‐NOARG; 10–500 μm), a specific inhibitor of nitric oxide synthase (NOS), neomycin (10–500 μm), a phospholipase C inhibitor and indomethacine (1–10 μm), a non‐selective COX inhibitor, significantly inhibited the relaxations induced by ethanol. In contrast ouabain (10–100 μm), an inhibitor of Na+–K+‐ATPase, failed to cause significant alteration on these relaxations in the same tissue. The results of the present study suggest that the inhibitory effect of ethanol on the mouse esophagus may be direct effect of ethanol on the muscle tissue rather than neuronal effect. In addition, intracellular but not extracellular Ca2+ may have a role on ethanol‐induced relaxations in isolated mouse esophageal strips. Potassium channels and nitric oxide may also have a role on these relaxations. Similarly, phospholypase C and arachidonic acid pathways may contribute the relaxations to ethanol. However Na+–K+‐ATPase may not have a role on relaxations induced by ethanol in the mouse esophagus.