Pharmacological evidence for alpha-2 adrenoceptor heterogeneity: differential binding properties of [3H]rauwolscine and [3H]idazoxan in rat brain

J Pharmacol Exp Ther. 1987 Jun;241(3):1092-8.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Binding Sites
  • Brain / metabolism*
  • Dioxanes / metabolism*
  • Dioxins / metabolism*
  • Dopamine / pharmacology
  • Epinephrine / pharmacology
  • Idazoxan
  • Kinetics
  • Lung / metabolism
  • Male
  • Norepinephrine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / metabolism*
  • Serotonin / pharmacology
  • Spiperone / metabolism
  • Tissue Distribution
  • Yohimbine / metabolism*


  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Dioxanes
  • Dioxins
  • Receptors, Adrenergic, alpha
  • Yohimbine
  • Serotonin
  • Spiperone
  • Dopamine
  • Norepinephrine
  • Idazoxan
  • Epinephrine