Ethanol-induced relaxation of mouse esophagus: subcellular mechanisms.
Ethanol (164 mm) produced reproducible relaxations in isolated mouse esophageal strips. Hexamethonium (10-500 microm), a ganglionic blocking agent, and lidocaine (10-100 microm), a local anesthetic agent, failed to affect the relaxations induced by ethanol in the mouse esophagus. Although verapamil (10-500 microm), a selective blocker of L-type Ca(2+) channels, failed to affect the relaxations to ethanol, ruthenium red (10-100 microm), a selective blocker of ryanodine receptors (intracellular Ca(2+) channels), and cyclopiazonic acid (1-10 microm), a selective blocker of sarcoplasmic reticulum Ca(2+) ATPase (SERCA), significantly inhibited these relaxations. In addition, tetraethylammonium (10-100 microm), a potassium-selective ion channel blocker and N(omega)-nitro-l-arginine (l-NOARG; 10-500 microm), a specific inhibitor of nitric oxide synthase (NOS), neomycin (10-500 microm), a phospholipase C inhibitor and indomethacine (1-10 microm), a non-selective COX inhibitor, significantly inhibited the relaxations induced by ethanol. In contrast ouabain (10-100 microm), 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 Ca(2+) 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.
Döndaş
Naciye Yaktubay
NY
Department of Pharmacology, Cukurova University, Adana, Turkey. yakdas25@cu.edu.tr <yakdas25@cu.edu.tr>
Kaya
Derya
D
Kaplan
Mahir
M
Ertuğ
Peyman
P
Singirik
Ergin
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D015203:Reproducibility of Results
D015221:Potassium Channels; D009569:Nitric Oxide; D000431:Ethanol; D002118:Calcium