A comparative study of postsynaptic alpha2-adrenoceptors of the dog mesenteric and rat femoral veins.

The aim of the present study was to compare the subtype of postjunctional alpha2-adrenoceptors of canine mesenteric and rat femoral veins. To check whether the presence of alpha1-adrenoceptors in both tissues might interfere with alpha2-adrenoceptor-mediated effects, the experiments were carried out under two experimental conditions: without and with alpha1-adrenoceptor blockade. The selective and irreversible alpha1-adrenoceptor antagonist phenoxybenzamine (30 nM) was used to eliminate alpha1-adrenoceptors. The pA2 values for the antagonism exerted by eight alpha-adrenoceptor antagonists (rauwolscine, yohimbine, RX821002, WB4101, idazoxan, phentolamine, spiroxatrine and prazosin) against the highly selective alpha2-adrenoceptor agonist UK-14,304 were determined under these two experimental conditions and correlated with pKi values of the same antagonists at cloned human alpha2A-, alpha2B- and alpha2C-adrenoceptors expressed in Chinese hamster lung cells and at the alpha2D-adrenoceptors in the rat submaxillary gland or the bovine pineal gland. In most of the experiments carried out in the canine mesenteric vein, the concentration-response curves for UK-14,304 were biphasic; the first phase was antagonized by low concentrations (2-50 nM) of the antagonists used except prazosin, while the second one was antagonized by 30 nM of either prazosin or phenoxybenzamine. In the rat femoral vein, the concentration-response curves to UK-14,304 were monophasic. In either tissue, the pA2 values obtained in untreated preparations and in preparations pretreated with phenoxybenzamine were not significantly different, showing that effects resulting from the activation of alpha1-adrenoceptors can be avoided simply by using low concentrations of the highly selective alpha2-adrenoceptor agonist UK-14,304. The correlation between pA2 and pKi values showed that, while in the canine mesenteric vein the postjunctional alpha2-adrenoceptors resemble alpha2A-adrenoceptors more closely, in the rat femoral vein they are more closely related to alpha2D-adrenoceptors. In either species, therefore, they belong to the genetic alpha2A/D type of alpha2-adrenoceptor.