Pharmacologic implications of alpha-adrenoreceptor interactive parameters for epinephrine enantiomers in the rat vas deferens |
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Authors: | P J Rice D D Miller T D Sokoloski P N Patil |
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Affiliation: | College of Pharmacy, Ohio State University, Columbus 43210. |
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Abstract: | After alkylation of a fraction of the total alpha-adrenoreceptors by phenoxybenzamine in rat vas deferens, the dissociation constants of (-)- and (+)-epinephrine in functional studies were 7 X 10(-7) M and 2 X 10(-5) M, respectively. In the adrenoreceptor-containing tissue fraction, when 3H-labeled WB4101 was used as the interacting ligand, for each enantiomer two affinity sites were found. Only the low-affinity dissociation constant for each isomer correlates with the constant obtained from the functional studies. If the change in Gibb's free energy, delta G degrees, is calculated from the low-affinity binding constants, the values -8.1 and -6.2 kcal/mol for (-)- and (+)-isomer, respectively, are obtained. The small difference in the value between isomers is consistent with the view that the benzylic hydroxyl group of the (-)-isomer forms a hydrogen bond with the receptor. The interaction of epinephrine with this receptor appears to be driven largely by the entropy of the drug-receptor interaction with only a small nonstereoselective contribution from the enthalpy of interaction. |
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Keywords: | affinity efficacy dissociation constants steroselectivity entropy enthalpy receptor interaction |
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