Investigation of the subtypes of α2-adrenoceptor mediating prejunctional inhibition in rat atrium and cerebral cortex

We have investigated the subtype of alpha(2)-adrenoceptor mediating prejunctional inhibition of neurotransmission in rat atrium in comparison with the alpha(2)-adrenoceptor mediating prejunctional inhibition in rat cerebral cortex. In rat atrium and cerebral cortex, prejunctional alpha(2)-adrenoceptors were investigated in terms of the ability of alpha(2)-adrenoceptor antagonists to increase the stimulation-evoked overflow of tritium in tissues pre-incubated with [H-3]-noradrenaline, The relatively non-selective alpha(2)-adrenoceptor antagonist yohimbine and the alpha(2)-adrenoceptor selective antagonist BRL 44408 had potencies in rat atrium which were similar to their potencies in rat cerebral cortex. The antagonists ARC 239, HV 723, WE 4101; prazosin, chlorpromazine and abanoquil, which have low affinity for alpha(2)-adrenoceptors, significantly increased stimulation-evoked overflow at lower concentrations in rat atrium than rat cerebral cortex. Antagonist potency at prejunctional alpha(2)-adrenoceptors was correlated with antagonist affinity at alpha(2)-adrenoceptor ligand binding sites in membranes of rat kidney (alpha(2B)) and submandibular gland (alpha(2D)), and human recombinant alpha(2C)-adrenoceptors labelled with [H-3]yohimbine. The correlation between ligand binding sites and the functional receptor in the rat cerebral cortex was significant only for the alpha(2)-adrenoceptor ligand binding site (r=0.87, n=8, P<0.01) as compared to the alpha(2B)-adrenoceptor (r=0.32 n.s.) or alpha(2C)-adrenoceptor (r=0.12, n.s.) ligand binding sites. The correlation between ligand binding sites and the functional receptor in the rat atrium was not significant for any ligand binding site, with r=0.64, 0.68 and 0.67 for the alpha(2D)-, the alpha(2B)- and the alpha(2C)-adrenoceptor ligand binding sites, respectively. It is concluded that the functional prejunctional alpha(2)-adrenoceptor of rat cerebral cortex closely resembles the alpha(2D)-adrenoceptor ligand binding site of rat submandibular gland, but the rat atrium may contain two subypes of prejunctional alpha(2)-adrenoceptor, alpha(2D) and another subtype, possibly alpha(2B) or alpha(2C).