Pre- and Post-junctional α-Adrenoceptor-mediated Responses in the Rat Gastric Fundus In-vitro

Abstract

Abstract The effects of α1-and α2-adrenoceptor agonists on smooth muscle tone and on cholinergic excitatory and non-adrenergic, non-cholinergic inhibitory responses to field stimulation have been investigated in the rat gastric fundus in-vitro. None of the α-adrenoceptor agonists tested, noradrenaline, phenylephrine, cirazoline, guanoxabenz or UK-14,304 showed any contractile effects at concentrations up to 30 μM. In preparations where tone was raised by barium (0.5-2 mM), the mixed α1-and α2-adrenoceptor agonist noradrenaline (0.01–10 μM), and the selective α1-adrenoceptor agonists cirazoline (0.01–10 μM) and phenylephrine (0.01–10 μM) produced concentration-dependent relaxations which were antagonized by the α1-adrenoceptor antagonist prazosin (0.01-1.0 μM). The selective α2-adrenoceptor agonists UK-14,304 (0.03–30 μM) and guanoxabenz (0.03–30 μM), had no relaxant effects in raised tone. UK-14,304 (0.03-1.0 μM) produced a concentration-dependent inhibition of cholinergic nerve-induced responses which was antagonized by the α2-adrenoceptor antagonist idazoxan (0.03-1.0 μM) but not by prazosin (0.03-1.0 μM). Noradrenaline (0.03-1.0 μM) also produced an inhibition of cholinergic nerve-induced responses which was antagonized by idazoxan (0.03–10 μM). A small component of the noradrenaline inhibitory effects was antagonized by prazosin (10%). Cirazoline (0.03-1.0 μM) produced a small inhibition of cholinergic nerve-induced responses which was antagonized by prazosin (0.03-1.0 μM). The prazosin-sensitive components of the inhibitory effects of noradrenaline and cirazoline occurred at concentrations which also produced post-junctional relaxation. UK-14,304 (0.03-1.0 μM) also attenuated non-adrenergic, non-cholinergic (NANC) inhibitory nerve-induced responses and this effect was antagonized by idazoxan (0.03-1.0 μM). The effects of α1-adrenoceptor agonists on NANC nerve-induced responses proved difficult to assess since these agonists caused post-junctional relaxation which itself reduced the size of the inhibitory nerve-induced responses. It is concluded that α-adrenoceptor mediated responses in the rat gastric fundus in-vitro consist of post-junctional α1-adrenoceptor-mediated relaxation of the smooth muscle and pre-junctional α2-adrenoceptor-mediated inhibition of both cholinergic excitatory and non-adrenergic, non-cholinergic inhibitory nerve-induced responses.