Involvement of alpha 2-adrenoceptors in mechanism of intragastric nicotine protection against ethanol injury in rat stomach.
To elucidate the role of alpha- and beta-adrenoceptors in the mechanism of intragastric nicotine protection against ethanol-induced gastric mucosal injury, the following studies were performed. At 0.5-hr prior to the injury study, rats were pretreated with: subcutaneous control, prazosin (0.5 mg/kg) or yohimbine (5 mg/kg) to block alpha 1- or alpha 2-adrenoceptors; or intraperitoneal control, metoprolol (2 mg/kg) or butoxamine (4 mg/kg) to block beta 1- or beta 2-adrenoceptors, respectively. At 1-hr intervals, rats received intragastric vehicle or nicotine (4 mg/kg) and 40% ethanol (10 ml/kg). Total lengths of the linear gastric corpus mucosal lesions were measured by an unbiased observer using a caliper. In a separate study, 0.5-hr after subcutaneous control or yohimbine (5 mg/kg), rats were treated with intragastric vehicle or nicotine (4 mg/kg). One hour later, gastric mucus volume, gastric juice volume and pH, and titratable acid in the gastric juice were measured. In the rat stomach, the intragastric nicotine protection against 40% ethanol-induced mucosal injury was not blocked by selective alpha 1-(prazosin), beta 1-(metoprolol), or beta 2-(butoxamine) adrenoceptor antagonists. The protection was significantly reduced although not completely abolished by selective alpha 2-(yohimbine) adrenoceptor antagonist. Yohimbine also significantly reduced basal and nicotine-stimulated increase in gastric mucus volume. These data suggest that alpha 2-adrenoceptors are involved in the protective effect of intragastric nicotine against 40% ethanol-induced gastric mucosal injury possibly by a mucus-dependent mechanism.
Endoh
K
K
Research Service, Sepulveda Veterans Administration Medical Center, California 91343.
Kao
J
J
Baker
M
M
Leung
F W
FW
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005750:Gastric Juice / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D009538:Nicotine