Alpha 1-adrenoceptor subtypes in the rat ventricular muscle.
Scatchard analyses of [3H]prazosin binding in rat ventricular muscle membranes showed biphasic curves, which identified alpha 1High- and alpha 1Low-affinity sites. The alpha 1High-affinity site was completely inhibited by 1 microM phenoxybenzamine. The displacement potencies of alpha 1-adrenergic antagonists were characterized by [3H]prazosin binding to alpha 1High- and alpha 1Low-affinity sites in the absence and presence of 1 microM phenoxybenzamine. The affinities of most chemicals for alpha 1Low-affinity sites were significantly lower than those for alpha 1High-affinity sites, but WB-4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane), arotinolol, cinanserin, nifedipine, and p-aminoclonidine had the same affinities for both alpha 1Low- and alpha 1High-affinity sites. These results show that two alpha 1-adrenoceptor subtypes, alpha 1High- and alpha 1Low-affinity, are present in the rat heart, and that there are physical variations in alpha 1-adrenoceptor binding sites, based on their selectivity to antagonists.
Department of Pharmacology, Niigata College of Pharmacy, Japan.
J
J
Kinami
H
H
Tsuchihashi
S
S
Baba
F
F
Mano
K
K
Maruyama
T
T
Nagatomo
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D006352:Heart Ventricles; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000378:metabolism / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012044:Regression Analysis
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D011224:Prazosin