title: Pharmacological evidence for alpha-2 adrenoceptor heterogeneity: differential binding properties of [3H]rauwolscine and [3H]idazoxan in rat brain.
abstract: In the preceding paper, we have reported that the two alpha-2 adrenoceptor antagonists, [3H]rauwolscine and [3H]idazoxan, exhibit markedly different autoradiographic distributions throughout rat brain. Although [3H]idazoxan labeling appears over brain regions receiving noradrenergic innervation, [3H]rauwolscine binding sites are localized most densely in several areas corresponding to dopaminergic terminal fields. We have presently characterized the pharmacological binding properties of high affinity [3H]rauwolscine and [3H]idazoxan labeled sites, using tissue preparation and incubation protocols which are identical to those used in the previous autoradiographic study. Endogenous monoamines inhibited radioligand binding with a rank order of potency of epinephrine = norepinephrine greater than dopamine greater than serotonin. Numerous dopaminergic compounds failed to inhibit either [3H]rauwolscine or [3H]idazoxan binding with high potency, and rauwolscine was a poor inhibitor of [3H]spiroperidol binding. Several adrenergic compounds which selectively label alpha-1 or beta adrenoceptors also exhibited low potency in inhibiting either radioligand. In contrast, alpha-2 adrenoceptor agonists and antagonists possessed high affinity for both [3H]rauwolscine and [3H]idazoxan labeled sites. Their relative potencies at the two sites differed, however. Whereas idazoxan was equipotent in inhibiting either [3H]rauwolscine or [3H]idazoxan binding, rauwolscine exhibited 10-fold higher affinity for its own labeled site. These pharmacological data are consistent with anatomical data presented in the preceding paper, which support the existence of a heterogenous population of alpha-2 adrenoceptors within rat brain, labeled entirely by [3H]idazoxan and only in part by [3H]rauwolscine.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D004146:Dioxanes / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D019329:Idazoxan; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism; D014018:Tissue Distribution; D015016:Yohimbine / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012701:Serotonin; D013134:Spiperone; D004298:Dopamine; D009638:Norepinephrine; D019329:Idazoxan; D004837:Epinephrine