Characterisation of alpha2-adrenoceptor subtypes involved in gastric emptying, gastric motility and gastric mucosal defence.
The effect of clonidine on ethanol-induced gastric mucosal damage, gastric emptying and gastric motility was compared. The clonidine-induced gastroprotective effect (0.03-0.09 micromol/kg, s.c.) was antagonised by yohimbine (5 micromol/kg, s.c.), prazosin (0.23 micromol/kg; alpha2B-adrenoceptor antagonist) and naloxone (1.3 micromol/kg, s.c.). Clonidine also inhibited the gastric emptying of liquid meal (0.75-3.75 micromol/kg, s.c.) and gastric motor activity (0.75 micromol/kg, i.v.) stimulated by 2-deoxy-D-glucose (300 mg/kg, i.v.). Inhibition of gastric emptying and motility was reversed by yohimbine (5 and 10 micromol/kg, s.c., respectively), but not by prazosin (0.23 micromol/kg, s.c.) or naloxone (1.3 micromol/kg, s.c.). Oxymetazoline-an alpha2A-adrenoceptor agonist-inhibited both gastric emptying (0.67-6.8 micromol/kg, s.c.) and motility (0.185-3.4 micromol/kg, i.v.), whereas it failed to affect gastric mucosal lesions. The results indicate that in contrast to the gastroprotective effect, which is mediated by alpha2B-adrenoceptor subtype, alpha2A-adrenoceptor subtype may be responsible for inhibition of gastric emptying and motility. However, the site of action (central, peripheral, both) remains to be established.
Fülöp
Katalin
K
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, 1089, Budapest, Nagyvárad tér 4, Hungary.
Zádori
Zoltán
Z
Rónai
András Z
AZ
Gyires
Klára
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005746:Gastric Emptying / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D009292:Narcotic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D009270:Naloxone; D000431:Ethanol; D010109:Oxymetazoline; D003000:Clonidine; D011224:Prazosin