Beta-adrenoceptor agonist stimulation of acid secretion by rat stomach in vitro is mediated by 'atypical' beta-adrenoceptors.

1. A previous study showed beta-adrenoceptor agonists stimulated acid secretion by rat stomach in vitro. The receptors could not be classed as either the beta 1- or beta 2-subtype. This study examines the effect of 2 'atypical' beta-agonists on acid secretion. 2. Basal and isoprenaline-stimulated acid secretion were compared in tissues bathed either in HEPES/O2- or HCO3-/CO2-buffer. Basal secretion was underestimated in HCO3- by an amount equal to the rate of base section. Tissues responded well in HEPES buffer and there was no base secretion following acid inhibition with SCH 28080. HEPES was used for the study. 3. SR 58611A stimulated acid in a concentration-related way (0.1-5 microM). Maximum response at 1 microM was equal to the response to a maximal concentration of isoprenaline. BRL 37344 (1 microM) also stimulated to the same extent. 4. Responses to isoprenaline (5 microM) and SR 58611A (1 microM) were reduced by propranolol (10 microM) but not by alprenolol (10 microM) or by practolol (12.5 microM) plus ICI 118551 (1 microM). 5. Exposure to SR 58611A (1 microM) led to desensitization to isoprenaline but not to bethanechol (1 microM) or histamine (50 microM). 6. We conclude that a HEPES/O2-buffer is advantageous when measuring gastric acid secretion in vitro and the stimulatory effect of beta-adrenoceptor agonists is mediated by 'atypical' receptors.