Variation in Sensitivity of α₁-Adrenoceptor Stimulants and α₁-Adrenoceptor Mechanisms in Rabbit Arteries

Abstract

Sensitivity (pD₂ value, negative logarithm of the molar concentration producing the half maximum response) and affinity (pK_A value, negative logarithm of dissociation constant) of norepinephrine were determined in 6 arteries from rabbits. A positive correlation was found in the pD₂ and pK_A values of norepinephrine. The slope was not significantly different from 1. The pD₂ and pK_P (a negative logarithm of dissociation constant of a partial agonist) values of tizanidine, an α₁-partial agonist, were also determined. There were positive correlations between the pD₂ and pK_P 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 α₁-adrenoceptors. The dissociation constants, KD values, and the maximum binding sites, B_max, 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, B_max varied considerably among rabbit arteries. There was a positive correlation between the logarithm of B_max 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 α₁-adrenoceptors as well as the receptor densities.