title: Heterogeneity between soluble human and rabbit splenic alpha 2-adrenoceptors.
abstract: The pharmacological and biochemical characteristics of soluble alpha 2-adrenoceptors were investigated to determine whether differences observed in membranes were maintained in solution and to probe the nature of any such differences. alpha 2-Adrenoceptors were solubilized from purified plasma membrane preparations of human and rabbit spleen using digitonin. [3H]yohimbine bound to one population of alpha 2-adrenoceptors in the preparations with dissociation constants of 2.4 nM and 7.8 nM respectively. The pharmacological profile of the alpha 2-adrenoceptors has been examined. Upon solubilization the affinity of the alpha 2-adrenoceptors for yohimbine was unchanged. In contrast, the potency of idazoxan and RX 811066 were increased, whereas the potency for prazosin (human only), phentolamine and WY 26392 was decreased 2-3-fold. The potency of the agonists oxymetazoline, UK 14304 and adrenaline were all reduced upon solubilization of alpha 2-adrenoceptors. The selectivity of yohimbine, idazoxan, RX 811066 and WY 26392 for human rather than rabbit alpha 2-adrenoceptors was maintained in solution. Possible sources of heterogeneity between human and rabbit alpha 2-adrenoceptors were investigated. The protein structure was probed by comparing the susceptibility of the receptors to inactivation by sulphydryl modifying agents. No differences were observed in the potency of N-ethylmaleimide or p-chloromercuribenzoate to inactivate the receptor. The carbohydrate component of the receptors was investigated using agarose-linked lectins. Rabbit splenic alpha 2-adrenoceptors had a lower affinity for the lectins wheatgerm agglutinin (Triticum vulgaris) and soybean (Glycine max) which bind the sugars N-acetyl d-glucosamine and N-acetyl d-galactosamine respectively. These findings suggest that heterogeneity of the alpha 2-adrenoceptor derives from its structural characteristics rather than its environment in the membrane.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D019329:Idazoxan; D037102:Lectins / Q000378:metabolism; D010109:Oxymetazoline / Q000494:pharmacology; D010646:Phentolamine / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011807:Quinolizines / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D012995:Solubility; D013154:Spleen / Q000032:analysis*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D015016:Yohimbine / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D037102:Lectins; D011807:Quinolizines; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D013439:Sulfhydryl Reagents; D015016:Yohimbine; D000068438:Brimonidine Tartrate; C038537:Wy 26392; D010109:Oxymetazoline; D011224:Prazosin; D019329:Idazoxan; D004837:Epinephrine; D010646:Phentolamine