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 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.
Gavin
K
K
Department of Physiology, Royal College of Surgeons, Dublin, Ireland.
Docherty
J R
JR
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003655:Decerebrate State; D004983:Ethanolamines / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism; D014991:Xylazine / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D004983:Ethanolamines; D018341:Receptors, Adrenergic, alpha-2; D014991:Xylazine; C016980:amidephrine; D010109:Oxymetazoline