Pre- and post-junctional alpha-adrenoceptor-mediated responses in the rat gastric fundus in-vitro

The effects of alpha 1- and alpha 2-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 alpha-adrenoceptor agonists tested, noradrenaline, phenylephrine, cirazoline, guanoxabenz or UK-14,304 showed any contractile effects at concentrations up to 30 microM. In preparations where tone was raised by barium (0.5-2 mM), the mixed alpha 1- and alpha 2-adrenoceptor agonist noradrenaline (0.01-10 microM), and the selective alpha 1-adrenoceptor agonists cirazoline (0.01-10 microM) and phenylephrine (0.01-10 microM) produced concentration-dependent relaxations which were antagonized by the alpha 1-adrenoceptor antagonist prazosin (0.01-1.0 microM). The selective alpha 2-adrenoceptor agonists UK-14,304 (0.03-30 microM) and guanoxabenz (0.03-30 microM), had no relaxant effects in raised tone. UK-14,304 (0.03-1.0 microM) produced a concentration-dependent inhibition of cholinergic nerve-induced responses which was antagonized by the alpha 2-adrenoceptor antagonist idazoxan (0.03-1.0 microM) but not by prazosin (0.03-1.0 microM). Noradrenaline (0.03-1.0 microM) also produced an inhibition of cholinergic nerve-induced responses which was antagonized by idazoxan (0.03-1.0 microM). A small component of the noradrenaline inhibitory effects was antagonized by prazosin (10%). Cirazoline (0.03-1.0 microM) produced a small inhibition of cholinergic nerve-induced responses which was antagonized by prazosin (0.03-1.0 microM). The prazosin-sensitive components of the inhibitory effects of noradrenaline and cirazoline occurred at concentrations which also produced post-junctional relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)