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Inhibition of Norepinephrine Transport and Reserpine Binding by Reserpine Derivatives
Author(s) -
Parti Rajesh,
Özkan Eric D.,
Harnadek Gordon J.,
Njus David
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05609.x
Subject(s) - reserpine , chemistry , catecholamine , norepinephrine , vesicle , tetrabenazine , chromaffin cell , stereochemistry , biochemistry , adrenal medulla , pharmacology , membrane , endocrinology , dopamine , biology
Reserpine, a competitive inhibitor of catecholamine transport into adrenal medullary chromaffin vesicles, consists of a trimethoxybenzoyl group esterified to an alkaloid ring system. Reserpine inhibits norepinephrine transport with a K i of ∼ 1 n M and binds to chromaffin‐vesicle membranes with a K D of about the same value. Methyl reserpate and reserpinediol, derivatives that incorporate the alkaloid ring system, also competitively inhibit norepinephrine transport into chromaffin vesicles with K i values of 38 ± 10 n M and 440 ± 240 n M , respectively. Similar concentrations inhibit [ 3 H]reserpine binding to chromaffin‐vesicle membranes. 3,4,5‐Trimethoxybenzyl alcohol and 3,4,5‐trimethoxybenzoic acid, derivatives of the other part of the reserpine molecule, do not inhibit either norepinephrine transport or [ 3 H]reserpine binding at concentrations up to 100 μ M . Moreover, trimethoxybenzyl alcohol does not potentiate the inhibitory action of methyl reserpate. Therefore, the amine binding site of the catecholamine transporter appears to bind the alkaloid ring system of reserpine rather than the trimethoxybenzoyl moiety. The more potent inhibitors are more hydrophobic compounds, suggesting that the reserpine binding site is hydrophobic.