Characteristics of binding of [3H]NE-100, a novel sigma-receptor ligand, to guinea-pig brain membranes

We examined the characteristics of binding of radiolabeled N,N-dipropyl-2-[4-methoxy-3-(2-phenyl-ethoxy)phenyl]- ethylamine monohydrochloride ([3H] NE-100), a highly potent and selective sigma-receptor ligand, to guinea-pig brain membranes. [3H]NE-100 showed saturable and reversible binding to sigma...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 1995-03, Vol.351 (3), p.244-251
Main Authors: Tanaka, M, Shirasaki, T, Kaku, S, Muramatsu, M, Otomo, S
Format: Article
Language:English
Subjects:
Animals
Anisoles - metabolism
Binding, Competitive - drug effects
Brain - metabolism
Guinea Pigs
In Vitro Techniques
Kinetics
Ligands
Male
Membranes - metabolism
Nucleotides - pharmacology
Phenytoin - pharmacology
Propylamines - metabolism
Receptors, sigma - metabolism
Subcellular Fractions - metabolism
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Summary:We examined the characteristics of binding of radiolabeled N,N-dipropyl-2-[4-methoxy-3-(2-phenyl-ethoxy)phenyl]- ethylamine monohydrochloride ([3H] NE-100), a highly potent and selective sigma-receptor ligand, to guinea-pig brain membranes. [3H]NE-100 showed saturable and reversible binding to sigma binding sites. A dissociation constant (Kd) and maximal numbers of binding sites (Bmax) obtained from Scatchard plot analysis were 1.2 +/- 0.1 nM and 1049.3 +/- 115.1 fmol/mg protein (n = 3), respectively. NE-100 was the most potent inhibitor of [3H]NE-100 binding among several structurally dissimilar sigma-receptor ligands, including haloperidol and (+)-pentazocine. (+)-Benzomorphanes had more than a 10-fold potent inhibitory activity over (-)-benzomorphanes, with regard to [3H]NE-100 binding. The binding of [3H]NE-100 was not influenced by histaminergic, dopaminergic, adrenergic, serotonergic cholinergic or glutaminergic agents at 10(-7) M. GTP-gamma-S and phenytoin also did not affect the binding of [3H]NE-100. A higher [3H]NE-100 binding was observed in the cerebellum and medulla oblongata. Except for the nuclear fraction, the highest level of [3H]NE-100 binding to subcellular fractions was observed in microsomal fractions. These results suggest that NE-100 selectively binds, with a high affinity, to sigma-1 binding sites in guinea-pig brain membranes, as an "antagonist".
ISSN:0028-1298
1432-1912
DOI:10.1007/bf00233243