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Molecular Pharmacology, Vol 16, 1-9, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Quantitative Resolution of Beta-Adrenergic Receptor Subtypes by Selective Ligand Binding: Application of a Computerized Model Fitting Technique

ARTHUR A. HANCOCK 1, ANDRE L. DELEAN 1, and ROBERT J. LEFKOWITZ 1

1 Howard Hughes Medical Institute Laboratory, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710

Frog myocardium appears to possess both beta1 and beta2 receptors, based on the potency order of several adrenergic agonists to compete for [3H]dihydroalprenolo1 binding. Selective beta blocking agents are able to distinguish two receptor subtypes in frog myocardium, but only one site in rat ventricle. Computer modeling using a PDP 11/45 indicates that all rat beta receptors are beta1, whereas only 15%-25% of frog ventricular beta receptors are of the beta1 subtype. Computerized curve fitting can provide a more accurate estimate of receptor parameters than currently available graphical methods of analysis.

Note:
ACKNOWLEDGMENTS A.D.L. wishes to thank Frank Starmer and Bruce Wright of the Department of Clinical Epidemiology, Duke University, for generously providing access and guidance to the PDP 11/45 computer. The numerical analyses underlying the computer program were performed by A.D.L. at the NIH, NICHD, ERRB, in collaboration with P. J. Munson and D. Rodbard.

Submitted on October 17, 1978
Accepted on January 23, 1979




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