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Molecular Pharmacology, Vol 6, 524-531, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

The Structure-Activity Relationships of Adrenergic Compounds That Act on the Adenyl Cyclase of the Frog Erythrocyte

O. M. ROSEN 1, JACK ERLICHMAN 1, and S. M. ROSEN 1

1 Departments of Medicine and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461

The structure-activity relationships were determined for adrenergic compounds which either activated or blocked the activation of a partially purified adenyl cyclase isolated from frog erythrocytes. The results suggested that the presence of a beta-hydroxyl group was essential for activity and that the potency of agonists as well as antagonists increased with the size of the substituent group of the amino nitrogen. In addition to the requirements for receptor affinity, compounds with intrinsic activity (agonists) had to have either OH or CH2OH substituents in both the m- and p-positions of the benzene ring. Since these structural requirements agreed well with those reported for intact tissue preparations, utilization of this relatively simple, cell-free preparation of adenyl cyclase may be a useful method for studying compounds with beta-adrenengic activity and for further defining the chemical nature of a beta-adrenergic receptor.

Note:
ACKNOWLEDGMENTS The authors are indebted to Drs. L. Goldberg, N. C. Moran, and B. L. Horecker for their critical review of the manuscript.

Submitted on March 2, 1970




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