Structure-binding-activity analysis of beta-adrenergic amines--I. Binding to the beta receptor and activation of adenylate cyclase

Bilezikian, J.P.; Dornfeld, A.M.; Gammon, D.E.

Biochemical Pharmacology 27(10): 1445-1454

1978


ISSN/ISBN: 0006-2952
PMID: 29638
DOI: 10.1016/0006-2952(78)90100-4
Accession: 068518471

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Abstract
Over 50 catecholamines and related analogs were tested for their ability to bind to the .beta.-adrenergic receptor and to activate adenylate cyclase in membranes of the turkey erythrocyte. Using [125I]hydroxybenzylpindolol, a radioligand that was successfully used to detect .beta.-adrenergic receptors, binding to erythrocyte membranes was highly specific and showed strict selectivity for (-) antipodes. Over a range of 4 log orders, the affinity of a compound for the .beta.-receptor correlated significantly with its ability to activate adenylate cyclase. Potency both for specific binding and adenylate cyclase activation was related to the size of the substituent on the secondary ethanolamine and to the configuration of the aromatic group. Full intrinsic activity required the presence of the catechol and .beta.-hydroxyl groups. These results confirm that [125I]hydroxybenzylpindolol is a direct probe for the detection of .beta.-adrenergic receptors and further delineate the structural requirements for occupation and activation of the .beta.-adrenergic receptor.