Molecular Pharmacology, Vol 18, 341-347, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Thermodynamics of Agonist and Antagonist Interactions with Mammalian -Adrenergic Receptors

¹ Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262

The thermodynamic parameters associated with the interactions of agonists and antagonists with -adrenergic receptors on membranes prepared from rat cerebral cortex, cerebellum, heart, and lung were determined. The binding of [¹²⁵I]iodohydroxybenzylpindolol (IHYP) and the inhibition of IHYP binding by agonists and antagonists were examined at temperatures between 50 and 25°C. The density of receptors was not affected by the temperature at which the incubation was performed but the affinity of the receptor for agonists and antagonists increased as the temperature of the assay was decreased. The change in the affinity of the receptor for agonists was greater in magnitude than was the change in the affinity of the receptor for antagonists. The binding of antagonists was characterized by small decreases in enthalpy and substantial increases in entropy. The thermodynamic changes associated with agonist interactions with -adrenergic receptors were characterized by large decreases in enthalpy and thermodynamically unfavorable decreases in entropy. In heart, lung, and cerebellum the affinities of agonists were decreased when assays were carried out in the presence of GTP. This nucleotide had no effect on the affinity of the -adrenergic receptor in the cerebral cortex for agonists or for antagonists in any of the tissues examined. In tissues where binding of agonists was affected by the presence of GTP, the changes in enthalpy and entropy were less negative in the presence of GTP than in its absence.

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