INVESTIGATION OF THE SUBTYPE OF ALPHA(2)-ADRENOCEPTOR MEDIATING PREJUNCTIONAL INHIBITION OF CARDIOACCELERATION IN THE PITHED RAT-HEART

1 We have investigated the subtype of alpha(2)-adrenoceptor mediating prejunctional inhibition of cardioacceleration in the pithed rat heart in comparison with alpha(2)-adrenoceptor ligand binding sites. 2 In pithed rats, prejunctional alpha(2)-adrenoceptors were investigated in terms of the ability of alpha(2)-adrenoceptor antagonists to shift the inhibitory potency of the alpha(2)-adrenoceptor agonist, xylazine, against the tachycardia to a single electrical stimulus given via the pithing rod. 3 Antagonist potency at prejunctional alpha(2)-adrenoceptors in pithed rat heart was correlated with antagonist affinity at alpha(2)-adrenoceptor ligand binding sites in membranes of rat kidney and submandibular gland labelled with [H-3]-yohimbine. 4 The correlation with the prejunctional alpha(2)-adrenoceptor in pithed rat heart was best for the alpha(2D)-adrenoceptor ligand binding site of rat submandibular gland (r = 0.98, n = 10, P < 0.0001), as compared to correlations with the alpha(2A)-adrenoceptor ligand binding site of human platelet (r = 0.90, n = 9, P < 0.001), the alpha(2B)-adrenoceptor ligand binding site of rat kidney (r = 0.82, n = 10, P < 0.01) and with published results for the alpha(2C)-adrenoceptor ligand binding site (r = 0.48, n = 6, NS). 5 It is concluded that the functional prejunctional alpha(2)-adrenoceptor of pithed rat heart closely resembles the alpha(2D)-adrenoceptor ligand binding site of rat submandibular gland.