title: Alpha-1 adrenoceptor subtypes in canine aorta.
abstract: The present study was designed to demonstrate the existence in canine aorta of alpha 1-adrenoceptor subtypes, alpha 1High and alpha 1Low, that have different binding affinities for 3H-prazosin and to assess the binding affinity of several drugs for each subtype by a displacement experiment. A radioligand binding assay with 3H-prazosin revealed the presence of two alpha 1-adrenoceptor subtypes in the canine aorta. One of them which has a high affinity for prazosin was designated as alpha 1High (Kd: 12.40 pM, Bmax: 21.88 fmol/mg protein), and the other type was designated as alpha 1Low (Kd: 506.03 pM, Bmax: 88.22 fmol/mg protein). The pKi values of several drugs for each subtype were determined, and all drugs used in the present study, except for benoxathian and chlorethylclonidine, showed significant differences between the pKi values for alpha 1High and those for alpha 1Low. Although it is difficult to characterize each alpha 1High and alpha 1Low into alpha 1A or alpha 1B by only the displacement potency, one structural characteristic to distinguish between alpha 1High and alpha 1Low could be evaluated.
authors.affiliation: Department of Pharmacology, Niigata College of Pharmacy, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: N
authors.initials: N
authors.lastname: Ohkura
authors.forename: Y
authors.initials: Y
authors.lastname: Yagi
authors.forename: T
authors.initials: T
authors.lastname: Nagatomo
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000737:chemistry*; D001665:Binding Sites; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism; D004285:Dogs; D010075:Oxathiins / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000317:Adrenergic alpha-Antagonists; D010075:Oxathiins; D011942:Receptors, Adrenergic, alpha; C051731:chlorethylclonidine; C050877:benoxathian; D003000:Clonidine; D011224:Prazosin