The impact of extracellular and intracellular Ca2+ on ethanol-induced smooth muscle contraction.
OBJECTIVE
To evaluate the impact of extracellular and intracellular Ca2+ on contractions induced by ethanol in smooth muscle.


METHODS
Longitudinal smooth muscle strips were prepared from the gastric fundi of mice. The contractions of smooth muscle strips were recorded with an isometric force displacement transducer.


RESULTS
Ethanol (164 mmol/L) produced reproducible contractions in isolated gastric fundal strips of mice. Although lidocaine (50 and 100 micromol/L), a local anesthetic agent, and hexamethonium (100 and 500 micromol/L), a ganglionic blocking agent, failed to affect these contractions, verapamil (1-50 micromol/L) and nifedipine (1-50 micromol/L), selective blockers of L-type Ca2+ channels, significantly inhibited the contractile responses of ethanol. Using a Ca(2+)-free medium nearly eliminated these contractions in the same tissue. Ryanodine (1-50 micromol/L) and ruthenium red (10-100 micromol/L), selective blockers of intracellular Ca2+ channels/ryanodine receptors; cyclopiazonic acid (CPA; 1-10 mumol/L), a selective inhibitor of sarcoplasmic reticulum (SR) Ca(2+)-ATPase; and caffeine (0.5-5 mmol/L), a depleting agent of intracellular Ca2+ stores, significantly inhibited the contractile responses induced by ethanol. In addition, the combination of caffeine (5 mmol/L) plus CPA (10 micromol/L), and ryanodine (10 micromol/L) plus CPA (10 micromol/L), caused further inhibition of contractions in response to ethanol. This inhibition was significantly different from those associated with caffeine, ryanodine or CPA. Furthermore the combination of caffeine (5 mmol/L), ryanodine (10 micromol/L) and CPA(10 micromol/L) eliminated the contractions induced by ethanol in isolated gastric fundal strips of mice.


CONCLUSIONS
Both extracellular and intracellular Ca2+ may have important roles in regulating contractions induced by ethanol in the mouse gastric fundus.
Döndaş
Naciye Yaktubay
NY
Department of Pharmacology, Faculty of Medicine, Cukurova University, 01330 Adana, Turkey. yakdas25@cu.edu.tr
Kaplan
Mahir
M
Kaya
Derya
D
Singirik
Ergin
E
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005748:Gastric Fundus / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007211:Indoles; D019837:Ryanodine Receptor Calcium Release Channel; D012430:Ruthenium Red; D012433:Ryanodine; D002110:Caffeine; D000431:Ethanol; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid