ALPHA-2A ADRENOCEPTORS AND NONADRENERGIC IDAZOXAN BINDING-SITES IN CALF BRAIN AND RETINA ARE DISTINCT FROM THOSE IN HUMAN BRAIN

Alpha2 Adrenoceptors in membrane preparations of human and calf fronta l cortex and of calf retina can be labelled by the antagonists [H-3]id azoxan, [H-3]rauwolscine and [H-3]RX 821002. Present and previous data indicate that [H-3]idazoxan possesses the highest affinity for the al pha2 adrenoceptors in the calf tissues, whereas [H-3]rauwolscine displ ays the highest affinity for those in the human frontal cortex. Compet ition binding experiments with adrenergic and serotonergic drugs furth er support the notion that the alpha2 adrenoceptors in calf frontal co rtex and retina are similar, but distinct from the receptors in human frontal cortex. The alpha2 adrenoceptors in the three investigated tis sues display low affinity for the antagonist prazosin, which suggests that they all belong to the alpha2A subclass. The competition binding curves of the alpha2A adrenoceptor subtype-selective agonist oxymetazo line 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 alpha2 adrenoceptors to G proteins. The different bin ding characteristics of the alpha2A adrenoceptors from the investigate d human and bovine tissues are likely to reflect species-related diffe rences in protein structure. [H-3]Idazoxan binds also to non-adrenergi c sites in membrane preparations from the three tissues. However, the affinity of [H-3]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 t o differences in protein structure or even to differences in gene-prod uct.