A comparative study of postsynaptic alpha(2)-adrenoceptors of the dog mesenteric and rat femoral veins

The aim of the present study was to compare the subtype of postjunctional a lpha(2)-adrenoceptors of canine mesenteric and rat femoral veins. To check whether the presence of alpha(1)-adrenoceptors in both tissues might interf ere with alpha(2)-adrenoceptor-mediated effects, the experiments were carri ed out under two experimental conditions: without and with alpha-adrenocept or blockade. The selective and irreversible alpha-adrenoceptor antagonist p henoxybenzamine (30 nM) was used to eliminate alpha(1)-adrenoceptors. The p A(2), values for the antagonism exerted by eight alpha-adrenoceptor antagon ists (rauwolscine, yohimbine, RX821002, WB4101, idazoxan, phentolamine, spi roxatrine and prazosin) against the highly selective alpha(2)-adrenoceptor agonist UK-14,304 were determined under these two experimental conditions a nd correlated with pK(i) values of the same antagonists at cloned human alp ha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors expressed in Chinese hamste r lung cells and at the alpha(2D)-adrenoceptors in the rat submaxillary gla nd or the bovine pineal gland. In most of the experiments carried out in the canine mesenteric vein, the c oncentration-response curves for UK-14,304 were biphasic; the first phase w as antagonized by low concentrations (2-50 nM) of the antagonists used exce pt prazosin, while the second one was antagonized by 30 nM of either prazos in or phenoxybenzamine. In the rat femoral vein, the concentration-response curves to UK14,304 were monophasic. In either tissue, the pA(2), values obtained in untreated preparations and in preparations pretreated with phenoxybenzamine were not significantly dif ferent, showing that effects resulting from the activation of alpha(1)-adre noceptors can be avoided simply by using low concentrations of the highly s elective alpha(2)-adrenoceptor agonist UK-14,304. The correlation between p A(2), and pK(i), values showed that, while in the canine mesenteric vein th e postjunctional alpha(2)- adrenoceptors resemble alpha(2A)-adrenoceptors m ore closely, in the rat femoral vein they are more closely related to alpha (2D)-adrenoceptors. In either species,therefore, they belong to the genetic alpha(2A/D) type of alpha(2)-adrenoceptor.