Identification of alpha 1 adrenergic receptors in rabbit aorta with [125I] BE2254.
Alpha-adrenergic receptors may play an important role in regulating vascular tone and reactivity. To study alpha-adrenergic receptors in blood vessels, we have developed a method to characterize and quantitate alpha-adrenergic receptors in a particulate fraction of individual rabbit aortas using the high specific activity alpha antagonist [125I] BE2254. [125I] BE2254 specifically labels a single class of binding sites with a dissociation constant of 286 pM and a maximal binding capacity of 16.7 fmoles/mg protein. Catecholamines compete for [125I] BE2254 binding stereospecifically and with the characteristic alpha-adrenergic potency series of (-)epinephrine greater than or equal to (-)norepinephrine much greater than (-)isoproterenol. The alpha 1-selective antagonist prazosin (KD = 0.7 nM) is much more potent in competing for [125I] BE2254 binding than is the alpha 2-selective antagonist yohimbine (KD = 1000 nM), which suggests that the alpha adrenergic receptor identified is predominantly of the alpha 1 subtype. Also, the dissociation constants from these binding studies were in good agreement with those reported in rabbit aorta from classical pharmacological experiments where contraction was found to be mediated via alpha 1 receptors. This extension of radioligand binding techniques to individual rabbit aortas should simplify the study of vascular alpha adrenergic receptor regulation, and provide a basis for broadening the understanding of vascular alpha adrenergic receptors.
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D007545:Isoproterenol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism*; D010646:Phentolamine / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D044024:Tetralones; D015016:Yohimbine / Q000378:metabolism
D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; D015016:Yohimbine; C010652:BE 2254; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine