Investigation of the subtype of alpha(2)-adrenoceptor mediating pressor responses in the pithed rat

We have investigated the subtype of alpha(2)-adrenoceptor mediating postjunctional presser responses in the pithed rat in comparison with alpha(2)-adrenoceptor ligand binding sites. In pithed rats, postjunctional alpha(2)-adrenoceptors were investigated in terms of the ability of alpha(2)-adrenoceptor antagonists to shift the presser potency of the alpha(2)-adrenoceptor agonist xylazine. Antagonist potency at postjunctional alpha(2)-adrenoceptors in the pithed rat was correlated with antagonist affinity at alpha(2)-adrenoceptor ligand binding sites in membranes of rat kidney (alpha(2B)), Sf9 cells expressing human recombinant receptors (alpha(2C)) and rat submandibular gland (alpha(2D)) labelled with [H-3]yohimbine. The correlation with the postjunctional alpha(2)-adrenoceptor mediating presser responses in the pithed rat was better for the alpha(2D)-adrenoceptor ligand binding site of rat submandibular gland (r = 0.95, n = 9, P < 0.0001) and the alpha(2B)-adrenoceptor ligand binding site of rat kidney (r = 0.90, n = 9, P < 0.001) than with the human recombinant alpha(2C)-adrenoceptor ligand binding site (r = 0.81, n = 9, P < 0.01). When the presser potencies of three additional antagonists were included in the correlations for alpha(2B)- and alpha(2D)-sites only, the correlation with alpha(2D)-adrenoceptor ligand binding site of rat submandibular gland (r = 0.91, n = 12, P < 0.0001) was much better than with the alpha(2B)-adrenoceptor ligand binding site of rat kidney (r = 0.77, n = 12, P < 0.01). It is concluded that the functional postjunctional alpha(2)-adrenoceptors mediating presser responses in the pithed rat most closely resemble the alpha(2D)-adrenoceptors subtype.