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

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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.