Variation in sensitivity of alpha 1-adrenoceptor stimulants and alpha 1-adrenoceptor mechanisms in rabbit arteries.
Sensitivity (pD2 value, negative logarithm of the molar concentration producing the half maximum response) and affinity (pKA value, negative logarithm of dissociation constant) of norepinephrine were determined in 6 arteries from rabbits. A positive correlation was found in the pD2 and pKA values of norepinephrine. The slope was not significantly different from 1. The pD2 and pKP (a negative logarithm of dissociation constant of a partial agonist) values of tizanidine, an alpha 1-partial agonist, were also determined. There were positive correlations between the pD2 and pKP values of tizanidine and also between the two pD2 values of norepinephrine and tizanidine. The slopes were not significantly different from 1. These results suggest that the regional differences in pD2 values of norepinephrine and tizanidine in the arteries are partly due to the affinity and suggest that both drugs interact with one recognition site in the alpha 1-adrenoceptors. The dissociation constants, KD values, and the maximum binding sites, Bmax, for [125I]-HEAT were also estimated by Scatchard analysis of the specific binding of [125I]-HEAT to the membrane fractions from rabbit arteries. The KD values for [125I]-HEAT were also identical. However, Bmax varied considerably among rabbit arteries. There was a positive correlation between the logarithm of Bmax and the pD2 values for norepinephrine. The present results suggest that the regional difference in the pD2 values for norepinephrine in rabbit arteries is due to variations in the affinities to the alpha 1-adrenoceptors as well as the receptor densities.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
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Takayanagi
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Onozuka
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Koike
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001158:Arteries / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D044024:Tetralones
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007457:Iodine Radioisotopes; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; C010652:BE 2254; D009638:Norepinephrine