No evidence for temperature-dependent changes in the pharmacological specificity of? 1- adrenoceptors

Publisher Website
Google Scholar
Abstract
In rabbit lung membranes known to contain both β1- and β2-adrenoceptors it was studied whether changes in incubation temperature may affect binding characteristics and/or selectivity of β1- and β2-adrenoceptor drugs. For this purpose inhibition of binding of the highly specific β-adrenoceptor radioligand (±)-125iodocyanopindolol (ICYP) by β1- and β2-selective as well as non-selective drugs was determined at incubation temperatures of 37° C and 18° C and analyzed by Hofstee-plots. The density of β-adrenoceptors in rabbit lung membranes was identical independently of the incubation temperature. Atboth incubation temperatures β1- and β2-selective drugs showed biphasic displacement curves and non-linear Hofstee-plots, while inhibition of binding by the non-selective drugs resulted in monophasic displacement curves with linear Hofstee-plots. With decreasing temperature affinity of antagonists to β-adrenoceptors increased only slightly, while affinity of agonists increased markedly. Forall β1- and β2-selective drugs thesame ratio β1-/β2-adrenoceptors was calculated from the Hofstee-plots independently of the incubation temperature: It amonunted to about 80% β1- and 20 % β2-adrenoceptors in rabbit lung. At an incubation temperatur of 37°C the displacement curve of the agonist isoprenaline was biphasic in the absence of GTP with a non-linear Hofstee-plot indicating that at 37°C isoprenaline binds to high and low affinity states of the β-adrenoceptors in rabbit lung. At 18°C, however, β-adrenoceptors do not form the high affinity GTP-sensitive complex with agonists, since GTP had no influence on isoprenaline displacement curves. It is concluded that a decrease in the incubation temperature of ICYP binding assay from 37°C to 18°C does neither alter the relative amount of β1- and β2-adrenoceptors in rabbit lung membranes nor the selectivity of β1- and β2-selective adrenoceptor drugs.

This publication has 31 references indexed in Scilit: