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

Abstract

We have investigated the subtype of alpha 2-adrenoceptor mediating postjunctional pressor 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 pressor 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 [3H]yohimbine. The correlation with the postjunctional alpha 2-adrenoceptor mediating pressor 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 pressor 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 pressor responses in the pithed rat most closely resemble the alpha 2D-adrenoceptors subtype.