Comparison of alpha-2 adrenergic receptors and their regulation in rodent and porcine species.

The alpha-2 adrenergic antagonist [3H]yohimbine (YOH) and the alpha-2 agonist [3H]p-aminoclonidine (PAC) saturably label high-affinity binding sites in the submandibular gland from 3-week-old rats and 5-week-old pigs and in the lung from neonatal rats and 5-week-old pigs. [3H]YOH had KD values of 5.5, 1.8, 0.45 and 0.22 nM in the rat gland and lung and porcine gland and lung, respectively. KD values of 2.4, 5.3 and 1.3 nM were found for [3H]PAC in rodent and pig submandibular gland and pig lung, respectively. Both 3H-ligands labeled approximately the same density of sites within each tissue except in the rat lung in which [3H]PAC binding was too low to reliably estimate. In all cases the pharmacologic profile was indicative of an alpha-2 adrenergic receptor site. However, the Ki of yohimbine vs. [3H]PAC was 30- to 140-fold higher for the rodent relative to the porcine species. GTP decreased the affinity of (-)-epinephrine and PAC at [3H]YOH-labeled sites in the pig gland and lung, but did not shift the affinity of epinephrine in the rat gland. These results suggest the possibility of subtype or species differences for the alpha-2 receptor. The Ki values of the antagonists YOH and phentolamine were different at [3H]PAC and [3H]YOH sites. GTP caused a dose-dependent reduction in [3H]PAC binding in the porcine submandibular gland and lung. At 10 microM GTP, this loss was due to a decrease in 3H-agonist affinity, but not density.(ABSTRACT TRUNCATED AT 250 WORDS)