Relaxant Effects of α-Adrenoceptor Agonists in the Rat Isolated Gastric Fundus

Abstract

— In rat gastric fundus preparations with tone raised by the addition of barium chloride or carbachol, and in the presence of propranolol (2 μM) to prevent β‐adrenoceptor mediated effects, the adrenoceptor agonists noradrenaline, adrenaline, α‐methylnoradrenaline, isoprenaline, cirazoline and phenylephrine all caused concentration‐related relaxant responses. Relaxations to the catecholamines were poorly antagonized by prazosin (0.01‐1 μM) resulting in the slopes of Schild plots being less than unity, low pA₂ values for prazosin against the catecholamines and a clear relaxant effect of the catecholamines even in the presence of 1 μM prazosin. The prazosin‐resistant relaxations were unaffected by higher concentrations of prazosin (2 μM) and propranolol (30 μM) or by further additions of idazoxan (1 μM) or haloperidol (30 μM). The relaxations were not due to a non‐specific effect of the catechol nucleus since neither dihydroxyphenylethylene glycol (DOPEG) nor dihydroxyphenylacetic acid (DOPAC) produced relaxant effects at concentrations upto 300 μM. In contrast to the results with the catecholamines, prazosin was a potent antagonist of the relaxant effect of cirazoline and phenylephrine, although the antagonism was difficult to quantify due to a lowering of the slope of the concentration response curves to cirazoline and phenylephrine with the higher concentrations of prazosin (0.1 and 1.0 μM). In conclusion postjunctional relaxatory effects of catecholamines in the rat gastric fundus are mediated partly via α₁‐adrenoceptors and partly via an atypical adrenoceptor.