Alpha 2A adrenoceptors and non-adrenergic idazoxan binding sites in calf brain and retina are distinct from those in human brain.
alpha 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 alpha 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 alpha 2 adrenoceptors in calf frontal cortex and retina are similar, but distinct from the receptors in human frontal cortex. The alpha 2 adrenoceptors in the three investigated tissues display low affinity for the antagonist prazosin, which suggests that they all belong to the alpha 2A subclass. The competition binding curves of the alpha 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 alpha 2 adrenoceptors to G proteins. The different binding characteristics of the alpha 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.
Department of Protein Chemistry, Vrije Universiteit Brussel, St. Genesius-Rode, Belgium.
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Van Liefde
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Vauquelin
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De Keyser
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JP
De Backer
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De Vos
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D013045:Species Specificity; D015016:Yohimbine / Q000378:metabolism
D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C058525:2-methoxyidazoxan; D019329:Idazoxan