α 2A Adrenoceptors and non-adrenergic idazoxan binding sites in calf brain and retina are distinct from those in human brain

Abstract

α 2 Adrenoceptors in membrane preparations of human and calf frontal cortex and of calf retina can be labelled by the antagonists [ 3H]idazoxan, [ 3H]rauwolscine and [ 3H]RX 821002. Present and previous data indicate that [ 3H]idazoxan possesses the highest affinity for the α 2 adrenoceptors in the calf tissues, whereas [ 3H]rauwolscine displays the highest affinity for those in the human frontal cortex. Competition binding experiments with adrenergic and serotonergic drugs further support the notion that the α 2 adrenoceptors in calf frontal cortex and retina are similar, but distinct from the receptors in human frontal cortex. The α 2 adrenoceptors in the three investigated tissues display low affinity for the antagonist prazosin, which suggests that they all belong to the α 2A subclass. The competition binding curves of the α 2A adrenoceptor subtype-selective agonist oxymetazoline are shallow, but undergo a rightward shift and steepening in the presence of GTP. The shallow curves can therefore be attributed to the coupling of the α 2 adrenoceptors to G proteins. The different binding characteristics of the α 2A adrenoceptors from the investigated human and bovine tissues are likely to reflect species-related differences in protein structure. [ 3H]Idazoxan binds also to non-adrenergic sites in membrane preparations from the three tissues. However, the affinity of [ 3H]idazoxan for these sites in calf cortex and retina is appreciably lower than for those in human cortex. The species-related differences of the non-adrenergic idazoxan binding sites may be due to differences in protein structure or even to differences in gene-product.