Nonadrenergic [3H]idazoxan binding sites are physically distinct from alpha 2-adrenergic receptors.
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.
Michel
M C
MC
Department of Pharmacology, University of California San Diego, La Jolla.
Regan
J W
JW
Gerhardt
M A
MA
Neubig
R R
RR
Insel
P A
PA
Motulsky
H J
HJ
D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D004146:Dioxanes / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism*; D006801:Humans; D019329:Idazoxan; D066298:In Vitro Techniques; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011994:Recombinant Proteins
D004146:Dioxanes; D004147:Dioxins; D011942:Receptors, Adrenergic, alpha; D011994:Recombinant Proteins; D019329:Idazoxan