TY - JOUR T1 - Nonadrenergic [3H]idazoxan binding sites are physically distinct from alpha 2-adrenergic receptors. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 65 LP - 68 VL - 37 IS - 1 AU - M C Michel AU - J W Regan AU - M A Gerhardt AU - R R Neubig AU - P A Insel AU - H J Motulsky Y1 - 1990/01/01 UR - http://molpharm.aspetjournals.org/content/37/1/65.abstract N2 - We have recently demonstrated that the alpha 2-adrenergic radioligand [3H]idazoxan also labels additional sites that do not recognize catecholamines but bind with high affinity several chemically distinct drugs previously assumed to be highly selective for alpha 2-adrenergic receptors [Mol. Pharmacol. 35:324-330 (1989)]. We now have used three approaches to distinguish the nonadrenergic [3H]idazoxan sites from alpha 2-adrenergic receptors. (a) No nonadrenergic [3H]idazoxan binding sites were found in COS-7 cells transfected with the genes for the two known alpha 2-adrenergic receptor subtypes. (b) The ratio of alpha 2-adrenergic and nonadrenergic [3H]idazoxan sites in human platelet membranes varied considerably between various donors. (c) Highly purified platelet plasma membranes were enriched for alpha 2-adrenergic receptors but did not contain any nonadrenergic [3H]idazoxan binding sites. We conclude that the nonadrenergic [3H]idazoxan binding sites are not co-expressed with alpha 2-adrenergic receptors and at least in human platelets may be located in an intracellular compartment. ER -