Comparison between beta 3 and beta 2 adrenoceptor agonists as inhibitors of gastric acid secretion.
In order to investigate the role of beta 3 adrenoceptors in the regulation of gastric acid secretion we studied the effects of compound SR58611A (a selective agonist for atypical beta adrenoceptors), alone or in combination with beta-adrenoceptor antagonists, in the gastric fistula of a conscious cat. The effects of SR58611A were compared with those of clenbuterol, a selective agonist for beta 2 adrenoceptors. Intravenous infusion of SR58611A (0.3-3 mumol/kg/h) caused a dose-dependent, but partial, inhibition of the acid secretory response to 2-deoxy-D-glucose 100 mg/kg i.v., maximum effect not exceeding 40%. Clenbuterol (0.03-0.1 mumol/kg/h) caused a similar effect (maximum inhibition about 50%) at doses approximately 30 times lower. The acid secretion induced by the histamine H2-receptor agonist dimaprit (1 mumol/kg/h) was minimally affected by both beta adrenoceptor agonists. The inhibitory effect of SR58611A (3 mumol/kg/h) on 2-deoxy-D-glucose-induced acid secretion was not modified by pretreatment with the non-selective beta 1- and beta 2-adrenoceptor blocker propranolol, administered at doses (1.5 mumol/kg iv) that completely blocked the inhibitory effect of clenbuterol (0.1 mumol/kg/h). In contrast, bupranolol (10 mumol/kg i.v.) (a drug endowed with beta 3 antagonistic properties) prevented the inhibitory effects of both SR58611A and clenbuterol. The present data provide functional evidence that, besides beta 2-, also beta 3-adrenoceptors can have negative effects on gastric acid secretion, particularly when it is stimulated by indirect stimuli, like 2-deoxy-D-glucose. This gastric antisecretory activity may represent an additional mechanism for the physio-pharmacological control of gastric acid secretion.
Coruzzi
G
G
Institute of Pharmacology, University of Parma, Italy.
Spaggiari
S
S
Bertaccini
G
G
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002415:Cats; D002976:Clenbuterol / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D017442:Histamine Agonists / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000963:Antimetabolites; D017442:Histamine Agonists; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes; D003847:Deoxyglucose; C076252:amibegron; D002976:Clenbuterol; D017259:Dimaprit