Differential localization of alpha 2-adrenergic receptor subtypes in brain.
The pharmacological identification and characterization of subtypes of alpha 2-adrenergic receptors have been confirmed by molecular biological investigations. Using receptor autoradiographic techniques, it has been possible to show regions of the brain where alpha 2 agonist binding ([3H]para-aminoclonidine) is preferentially labeling the presumed guaninenucleotide-sensitive, high-affinity conformations of the alpha 2 receptor. Careful examination of autoradiograms generated using the tritiated antagonists yohimbine, idazoxan, and rauwolscine also indicates some disparity in the regions occupied by these radiolabeled ligands. Inhibition of [3H]rauwolscine binding with the subtype selective compounds, ARC-239, or oxymetazoline demonstrates that there are discrete regions of the brain where one receptor subtype predominates over the other. These studies indicate that previous investigations utilizing the agonist para-aminoclonidine as the ligand for obtaining labeling of alpha 2 receptors have overlooked some regions of binding due to the subtype selectivity of this ligand. A more complete localization of alpha 2-adrenergic receptors can be obtained using the tritiated antagonist rauwolscine, and the differential distribution of at least two subtypes of the alpha 2 receptor can be obtained by selective inhibition of this binding.
Neuropsychiatric Research Institute, Fargo, ND 58103.
J K
JK
Wamsley
M E
ME
Alburges
M A
MA
Hunt
D B
DB
Bylund
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000008:administration & dosage; D019329:Idazoxan; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D015016:Yohimbine; D006165:Guanylyl Imidodiphosphate; C016986:apraclonidine; D003000:Clonidine; D019329:Idazoxan