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 [3H]-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.