Open AccessConformational requirements for dopamine-induced vasodilation.
Author(s) -
Paul H. Volkman,
Jai D. Kohli,
Leon I. Goldberg,
Joseph G. Can,
Theresa Lee
Publication year - 1977
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.74.8.3602
Subject(s) - dopamine , chemistry , agonist , phenoxybenzamine , vasodilation , dopamine receptor , dopamine agonist , stereochemistry , receptor , pharmacology , medicine , endocrinology , biochemistry
The availability of a series of semi-rigid analogs of dopamine and epinine has made it possible to investigate the conformational requirements for action on dopamine and beta2-adrenergic vascular receptors. The analogs were screened for dopamine-agonist action by intra-arterial injections into the renal vascular bed and for beta2-adrenergic activity by similar injections into the femoral vascular bed in dogs pretreated with phenoxybenzamine. 2-Amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN) and its N-methyl derivative (analogous to the trans beta rotamer of dopamine) exhibited pronounced dopamine-agonist activity and minimal beta2-adrenergic activity. In contrast, the semi-rigid analog of the trans alpha rotamer of dopamine (2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene; A-5,6-DTN) and its N-methyl derivative exerted pronounced beta2-adrenergic activity but were inactive as dopamine agonists.6,7-Dihydroxytetrahydroisoquinoline, a semi-rigid analog of the cis beta rotamer of dopamine, did not produce renal vasodilation. These results indicate that a conformation of dopamine similar to that found in A-6,7-DTN is required for dopamine-vascular activity, while the conformation found in A-5,6-DTN is preferred for interaction with beta2-adrenergic receptors.