A mechanistic study of beta-adrenoceptor antagonists on ethanol-induced gastric damage.
The beta-adrenoceptor subtypes and the roles of myeloperoxidase and prostaglandin E2 in the anti-ulcer effect of beta-adrenoceptor antagonists were studied. A non-selective beta-adrenoceptor antagonist, propranolol, or selective beta-adrenoceptor antagonists, metoprolol (a beta 1-adrenoceptor antagonist) or butoxamine (a beta 2-adrenoceptor antagonist) were used. Propranolol given either intraperitoneally or orally reduced ethanol-induced mucosal damage and myeloperoxidase activity. Oral administration of butoxamine produced similar effects. The blood neutrophil count was increased after ethanol administration and this was reversed by the two drugs. Metoprolol did not affect myeloperoxidase activity, neutrophil count and mucosal damage under these experimental conditions. Oral administration of propranolol or butoxamine increased mucosal prostaglandin E2 level. It is concluded that the inflammatory responses to ethanol, as indicated by neutrophil infiltration in gastric mucosa, can be specifically inhibited by drugs that block beta 2-adrenoceptors. This action would explain in part why propranolol and butoxamine but not metoprolol lessened gastric damage. In addition, oral administration of propranolol and butoxamine increased the mucosal prostaglandin E2 level, which could partially contribute to their anti-ulcer effects.
Kaan
S K
SK
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
Mei
Q B
QB
Cho
C H
CH
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D015232:Dinoprostone / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000319:Adrenergic beta-Antagonists; D002492:Central Nervous System Depressants; D008054:Lipid Peroxides; D002078:Butoxamine; D000431:Ethanol; D008315:Malondialdehyde; D011433:Propranolol; D009195:Peroxidase; D008790:Metoprolol; D015232:Dinoprostone