Alpha 2-adrenoceptor subtypes and imidazoline-like binding sites in the rat brain

Br J Pharmacol. 1990 Apr;99(4):803-9. doi: 10.1111/j.1476-5381.1990.tb13010.x.


1. The binding of [3H]-yohimbine and [3H]-idazoxan to rat cortex and hippocampus is rapid, reversible and of high affinity. Saturation data indicate that a single population of binding sites exist for [3H]-yohimbine in the cortex (Bmax 121 +/- 10 fmol mg-1, protein; Kd 5.2 +/- 0.9 nM) and hippocampus (Bmax 72 +/- 6 fmol mg-1 protein; Kd 5.8 +/- 0.7 nM). [3H]-idazoxan labels one site in the cortex (Bmax 87 +/- 8 fmol mg-1 protein; Kd 4.1 +/- 0.9 nM) and hippocampus (Bmax 30 +/- 6 fmol mg-1 protein; Kd 3.5 +/- 0.5 nM), when 3 microM phentolamine is used to define non-specific binding. A second distinct [3H]-idazoxan binding site (Bmax 110 +/- 21 fmol mg-1 protein; Kd 3.6 +/- 0.07 nM) is identified in rat cortex if 0.3 microM cirazoline is used to define non-specific binding and 3 microM yohimbine is included to prevent binding to alpha 2-adrenoceptors. 2. Displacement studies indicate that the alpha 1-adrenoceptor antagonist prazosin and the 5-HT1 ligands 8-OH-DPAT, RU 24969 and methysergide differentiate [3H]-yohimbine binding into two components; a high and low affinity site. In contrast the displacement of [3H]-idazoxan by each ligand was monophasic. 3. The affinities of 8-OH-DPAT, RU 24969 and methysergide determined against [3H]-idazoxan binding to the cortex and hippocampus correlate significantly with the binding site displaying low affinity for prazosin and previously designated alpha 2A. In contrast, a poor correlation exists for the high affinity site for prazosin designated alpha 2B. 4. [3H]-idazoxan, in the presence of 3 microM yohimbine, labels a site that displays high affinity towards cirazoline, naphazoline and guanabenz, but low affinity towards clonidine, p-aminoclonidine, adrenaline, noradrenaline and the alpha 2-adrenoceptor antagonists yohimbine, rauwolscine, WY 26703 and BDF 6143. 5. The results of this study indicate that [3H]-yohimbine labels two sites; the alpha 2A- and alpha 2B-adrenoceptors whereas [3H]-idazoxan labels an alpha 2-adrenoceptor with a profile consistent with the alpha 2A-adrenoceptor subtype. In addition, [3H]-idazoxan labels an imidazoline binding site in the rat cortex that is pharmacologically distinct from alpha 2-adrenoceptors. The low affinity of clonidine and p-aminoclonidine indicates that the imidazoline-like binding site in rat cortex is different from the site labelled by [3H]-clonidine and [3H]-p-aminoclonidine in human, rat and bovine brain stem, providing evidence of potential heterogeneity within this class of binding sites.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Brain Chemistry / drug effects*
  • Cattle
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dioxanes / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Idazoxan
  • Imidazoles / pharmacology*
  • Imidazoline Receptors
  • In Vitro Techniques
  • Indoles / metabolism
  • Kinetics
  • Male
  • Methysergide / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects*
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Drug / drug effects*
  • Receptors, Drug / metabolism
  • Tetrahydronaphthalenes / metabolism
  • Yohimbine / metabolism


  • Adrenergic alpha-Agonists
  • Dioxanes
  • Imidazoles
  • Imidazoline Receptors
  • Indoles
  • Receptors, Adrenergic, alpha
  • Receptors, Drug
  • Tetrahydronaphthalenes
  • 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole
  • Yohimbine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Methysergide
  • Idazoxan