Agonist binding to mammalian beta 1 and beta 2 adrenoceptors: modulation by guanine nucleotides and magnesium

Agonist interaction with beta 1 and beta 2 adrenoceptors in rat and rabbit lung has been examined using ligand binding techniques and the results are discussed in relation to current models of beta-adrenoceptor-adenylate cyclase coupling. Agonist binding has been assessed by examining the ability of isoprenaline or salbutamol to displace the labelled antagonist 3H-dihydroalprenolol (3H-DHA) from specific receptor sites. Beta 1 and beta 2 adrenoceptors, even within the same tissue, exhibited different ion and temperature requirements for guanine nucleotide modulation of agonist binding. Thus, in contrast to the situation at beta 2 sites, agonist binding to beta 1 adrenoceptors was only sensitive to GTP if incubations were performed at physiological temperatures in the presence of Mg++ ions. These findings suggest that there may be different receptor-effector coupling relationships between the two beta-adrenoceptor subtypes.