Characterization of catecholamine-mediated relaxations in rat isolated gastric fundus: evidence for an atypical β-adrenoceptor

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Abstract
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 β3-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 μm) were antagonized in a concentration-dependent manner by prazosin (0.01 to 1 μm), although this antagonism was weak and non-competitive in nature. Relaxant responses to isoprenaline, in the presence of prazosin (0.1 μm), were antagonized only by the highest concentration of propranolol (1 μm) giving a pKB of 6.3. BRL 37344 also relaxed the rat gastric fundus in the presence of prazosin (0.1 μm), and the responses to BRL 37344 were unaffected by propranolol (1 μm). 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 μm) between concentration-response curves also caused an 11 fold rightward shift in the response to isoprenaline. 4 In the presence of prazosin (0.1 μm) and propranolol (1 μm), 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 μm) and propranolol (1 μm) were antagonized by (±)-cyanopindolol (1 μm), with a pKB of 6.56. Responses to isoprenaline, under the same conditions, were antagonized in a competitive manner by (±)-cyanopindolol (0.1–1 μm), 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 β-adrenoceptors similar to ‘atypical’ β-adrenoceptors in rat adipocytes and other tissues are present in the rat gastric fundus.