The Binding of Agonists and Antagonists to Rat Lung Beta-Adrenergic Receptors as Investigated by Thermodynamics and Structure-activity Relationships

Abstract

Interaction of several agonists and antagonists with the relevant beta receptor were studied in vitro using rat lung membranes as beta-adrenergic receptor source. The influence of temperature, between 4°C and 37°C, on the ability of beta-adrenergic agonists and antagonists to displace (-)-[¹²⁵ I]iodocyanopindolol from beta-adrenergic receptors was checked. Thermodynamic parameters were calculated from the K_i values thus obtained. Lipophilicity of the twenty molecules was also measured using a RP-HPLC method. The results obtained show: the density of receptors was not affected by the temperature but their affinity for the twenty agonists and antagonists increased with decreasing temperature; the binding of agonists is enthalpy driven while that of antagonists is entropy driven, with the exception of the lipophilic agonist dobutamine; a single relationship between entropy and lipophilicity exists for all twenty compounds and would suggest that molecular structure and physicochemical properties account for the thermodynamics of binding.