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 po stjunctional presser responses in the pithed rat in comparison with al pha(2)-adrenoceptor ligand binding sites. In pithed rats, postjunction al 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 postjun ctional alpha(2)-adrenoceptors in the pithed rat was correlated with a ntagonist affinity at alpha(2)-adrenoceptor ligand binding sites in me mbranes of rat kidney (alpha(2B)), Sf9 cells expressing human recombin ant receptors (alpha(2C)) and rat submandibular gland (alpha(2D)) labe lled with [H-3]yohimbine. The correlation with the postjunctional alph a(2)-adrenoceptor mediating presser responses in the pithed rat was be tter for the alpha(2D)-adrenoceptor ligand binding site of rat submand ibular gland (r = 0.95, n = 9, P < 0.0001) and the alpha(2B)-adrenocep tor ligand binding site of rat kidney (r = 0.90, n = 9, P < 0.001) tha n with the human recombinant alpha(2C)-adrenoceptor ligand binding sit e (r = 0.81, n = 9, P < 0.01). When the presser potencies of three add itional antagonists were included in the correlations for alpha(2B)- a nd alpha(2D)-sites only, the correlation with alpha(2D)-adrenoceptor l igand binding site of rat submandibular gland (r = 0.91, n = 12, P < 0 .0001) was much better than with the alpha(2B)-adrenoceptor ligand bin ding site of rat kidney (r = 0.77, n = 12, P < 0.01). It is concluded that the functional postjunctional alpha(2)-adrenoceptors mediating pr esser responses in the pithed rat most closely resemble the alpha(2D)- adrenoceptors subtype.