title: Arylazide photoaffinity probe for alpha 2-adrenoceptors.
abstract: An arylazide photoaffinity probe for alpha 2-adrenoceptors has been developed and characterized. The compound, 3-methyl-6-chloro-9-azido-1H-2,3,4,5-tetrahydro-3-benzazepine (SKF 102229), had a Ki for the human platelet alpha 2-adrenoceptor of approximately 40 nM. Upon exposure to ultraviolet light, SKF 102229 irreversibly blocked the binding of [3H]yohimbine to both membrane bound and solubilized, partially purified, receptors. The extent of alpha 2-adrenoceptor blockade was dependent upon both the length of exposure to ultraviolet light and the concentration of SKF 102229. Typically, a 60% decrease in alpha 2-adrenoceptor number is obtained following 8 min of photolysis in the presence of 100 nM SKF 102229. The pharmacologic characteristics of the irreversible blockade produced by SKF 102229 were those of an alpha 2-adrenoceptor. Thus, photodependent, irreversible blockade of alpha 2-adrenoceptors by SKF 102229 was prevented by the concomitant presence of phentolamine or p-aminoclonidine but not by prazosin. Given its specificity and efficient blockade of the ligand binding site, SKF 102229 should prove useful for studies of the structure and function of alpha 2-adrenoceptors.
authors.forename: J W
authors.initials: JW
authors.lastname: Regan
authors.forename: R M
authors.initials: RM
authors.lastname: DeMarinis
authors.forename: R J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D000042:Absorption; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D010782:Photolysis; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D014316:Tritium; D014466:Ultraviolet Rays; D015016:Yohimbine / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D015016:Yohimbine; C016986:apraclonidine; C046823:SK&F 102229; D003000:Clonidine; D011224:Prazosin; D010646:Phentolamine