CHARACTERIZATION OF CATECHOLAMINE-MEDIATED RELAXATIONS IN RAT ISOLATED GASTRIC FUNDUS - EVIDENCE FOR AN ATYPICAL BETA-ADRENOCEPTOR

1 Experiments were carried out in order to characterize the receptors mediating relaxant responses to catecholamines in the rat gastric fundus. The effects of noradrenaline, isoprenaline and the 'atypical' or beta-3-adrenoceptor agonist, BRL 37344, on methacholine-induced tone were measured. Prazosin, propranolol and cyanopindolol were used as antagonists. 2 Relaxant responses to noradrenaline, in the presence of propranolol (1-mu-M) were antagonized in a concentration-dependent manner by prazosin (0.01 to 1-mu-M), although this antagonism was weak and non-competitive in nature. Relaxant responses to isoprenaline, in the presence of prazosin (0.1-mu-M), were antagonized only by the highest concentration of propranolol (1-mu-M) giving a pK(B) of 6.3. BRL 37344 also relaxed the rat gastric fundus in the presence of prazosin (0.1-mu-M), and the responses to BRL 37344 were unaffected by propranolol (1-mu-M). 3 Tachyphylaxis to BRL 37344 was observed, a second concentration-response curve being significantly shifted to the right. Exposure of tissues to BRL 37344 (1-mu-M) between concentration-response curves also caused an 11 fold rightward shift in the response to isoprenaline. 4 In the presence of prazosin (0.1-mu-M) and propranolol (1-mu-M), the rank order of potency of the agonists was: (-)-isoprenaline (1.0) > (-)-noradrenaline (0.39) > BRL 37344 (0.10). 5 Responses to BRL 37344 in the presence of prazosin (0.1-mu-M) and propranolol (1-mu-M) were antagonized by (+/-)-cyanopindolol (1-mu-M), with a pK(B) of 6.56. Responses to isoprenaline, under the same conditions, were antagonized in a competitive manner by (+/-)-cyanopindolol (0.1-1-mu-M), with the slope of a Schild plot close to unity and a pA2 value of 7.44. 6 The resistance to blockade by prazosin and propranolol and the antagonism by cyanopindolol of the responses mediated by isoprenaline and BRL 37344 suggest that atypical beta-adrenoceptors similar to 'atypical' beta-adrenoceptors in rat adipocytes and other tissues are present in the rat gastric fundus.