(−) [¹²⁵I] Iodopindolol Binding to β-Adrenergic Receptors in Tissues of the Rat with Particular Reference to the Characterization in Liver

Abstract

The high affinity β-adrenergic antagonist (-) [¹²⁵I] iodopindolol was used to characterize and quantitate β-adrenergic binding in liver and other tissues of the rat. Saturable, stereospecific binding with typical characteristics of β-adrenergic receptors was demonstrated in all tissues examined (liver, lung, heart, kidney, fat and brain).

Unlike the case with other radioactive ligands that have been used to measure β-adrenergic receptors, assays were possible in crude homogenates as well as in purified membranes. Specific binding was defined as [¹²⁵I]iodopindolol displaced by 0.1 mM isoproterenol. The percentage of [¹²⁵I]iodopindolol specifically bound was greater than with other labelled antagonist ligands and it ranged from 95–60% of total binding over [¹²⁵I]iodopindolol concentrations of 15–1000 pM. β-Adrenergic binding could be quantitated in liver of animals of all ages whereas previously quantitation in liver was possible only using rats less than 2 months of age. Binding capacities ranged from a low of approximately 6 fmol/mg in liver particles precipitated at 4500 g to approximately 550 fmol/mg in 4500 g lung particles. The Kd of binding obtained by kinetic analysis was similar in all tissues.

[¹²⁵I] Iodopindolol is a nearly ideal ligand for the quantitation of β-adrenergic receptors in various tissues of the rat. Because of its high affinity, stability and availability at high specific activity, this ligand should be especially useful in physiological studies requiring the accurate quantitation of receptor capacities.