ISSN:
1432-1912
Keywords:
Key words Sigma binding sites
;
NE-100
;
(N
;
N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy) phenyl]-ethylamine monohydrochloride)
;
Radiolabeled ligand binding
;
Brain
;
Guinea-pig
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 (B max) 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-γ-S and phenytoin also did not affect the binding of [3H]NE-100. A higher [3H]NE-100 binding was observed in the cerbellum 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”.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00233243
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