Development of an affinity ligand for purification of alpha 2-adrenoceptors from human platelet membranes.
Human platelets contain alpha 2-adrenoceptors which are negatively coupled to the enzyme adenylate cyclase. In order to better understand the interaction of this subtype of alpha receptor with this key enzyme, we have initiated a program to isolate and characterize the alpha 2-adrenoceptor. This report describes the synthesis and biological characterization of a series of molecules that were prepared as affinity ligands for this purpose. The best of these is 9-(allyloxy)-6-chloro-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 101253). This compound is an alpha 2-adrenoceptor antagonist, which was obtained by synthetic modification of 6-chloro-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 86466), a novel antagonist with high affinity for the alpha 2-receptor.
D000345:Affinity Labels / Q000138:chemical synthesis*; D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001792:Blood Platelets / Q000032:analysis*; D002462:Cell Membrane / Q000032:analysis; D006168:Guinea Pigs; D006801:Humans; D011942:Receptors, Adrenergic, alpha / Q000302:isolation & purification*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects; D015016:Yohimbine / Q000378:metabolism
D000345:Affinity Labels; D001552:Benzazepines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C036606:9-allyloxy-6-chloro-3-methyl-2,3,4,5-tetrahydro-1H-benzazepine; C039139:benalfocin