Characterization of [3H](±)carazolol binding to β-adrenergic receptors. Application to study of β-adrenergic receptor subtypes in canine ventricular myocardium and lung

99Citations
Citations of this article
9Readers
Mendeley users who have this article in their library.

Abstract

[3H](±)Carazolol, a newly available β-adrenergic receptor antagonist, has been used to characterize β-adrenergic receptor subtypes present in membrane vesicles derived from canine ventricular myocardium and canine lung. [3H](±)Carazolol binding is saturable, of high affinity, and is displaceable by β-adrenergic agents in accordance with their known pharmacological potencies. The interaction of carazolol with β-adrenergic receptors is stereospecific; the (-) stereoisomer demonstrates greater potency than the (+) stereoisomer. Kinetic analysis of [3H](±)carazolol interaction with β-adrenergic receptors suggests the presence of two phases of interaction, consistent with initial rapidly reversible 'low' affinity association of ligand with receptor, followed by isomerization to form a high affinity, slowly reversible complex. Through use of a [3H](±)carazolol binding assay based on the high affinity complex, pharmacological specificities of β-adrenergic receptor populations of canine myocardium and lung were quantified. Analysis using computer-assisted techniques suggests a β1/β2 receptor ratio of approximately 85%/15% for canine myocardium and 5%/95% for canine lung. In the absence of added guanine nucleotides, comparison of potencies of β-adrenergic agonists in the two membrane systems suggests significant β2 selectivity of l-isoproterenol and l-epinephrine, and non-selectivity of norepinephrine. In the presence of saturating levels of guanine nucleotides, comparison of agonist potencies confirms the non-selectivity of l-isoproterenol and l-epinephrine, and β1 selectivity of norepinephrine. These results demonstrate that the state of guanine nucleotide regulation of receptors should be defined when examining agonist selectivities for β-adrenergic receptor subtypes in vitro.

Cite

CITATION STYLE

APA

Manalan, A. S., Besch, H. R., & Watanabe, A. M. (1981). Characterization of [3H](±)carazolol binding to β-adrenergic receptors. Application to study of β-adrenergic receptor subtypes in canine ventricular myocardium and lung. Circulation Research, 49(2), 326–336. https://doi.org/10.1161/01.RES.49.2.326

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free