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Neomycin Is an Agonist at a Polyamine Site on the N‐Methyl‐D‐Aspartate Receptor
Author(s) -
Pullan L. M.,
Stumpo R. J.,
Powel R. J.,
Paschetto K. A.,
Britt M.
Publication year - 1992
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.1471-4159.1992.tb10099.x
Subject(s) - spermidine , polyamine , ifenprodil , neomycin , agonist , chemistry , binding site , spermine , antagonist , pharmacology , biochemistry , receptor , biology , enzyme , antibiotics
Neomycin appears as a full agonist and spermidine as a partial agonist at the site where polyamines enhance 1‐[1‐(2‐thienyl)cyclohexyl][ 3 H]piperidine ([ 3 H]TCP) binding on the N ‐methyl‐D‐aspartate (NMDA) receptor. Other aminoglycosides also enhance [ 3 H]TCP binding with efficacies roughly proportional to the number of primary amine groups. The polyamine antagonists ifenprodil and arcaine inhibit enhancement of [ 3 H]TCP binding by spermidine or neomycin. The inhibition of [ 3 H]TCP binding by arcaine is apparently competitively reduced by neomycin and spermidine, supporting a common site. Diethylenetriamine (previously described as a polyamine antagonist) may be a partial agonist. Enhancement by neomycin or spermidine is not additive to that of Mg 2+ , consistent with competition of Mg 2+ and spermidine or neomycin at the site where these compounds enhance [ 3 H]TCP binding. Polyamines also enhance the binding of the competitive antagonist 2 ‐ (2 ‐ carboxypiperazin ‐ 4 ‐ yl)[ 3 H]propyl ‐ 1 ‐ phosphonic acid ([ 3 H]CPP). Neomycin, which does not enhance [ 3 H]CPP binding, inhibits the enhancement by spermidine. That this site is distinct from the site where spermidine and neomycin increase [ 3 H]TCP binding is supported by different pharmacology. Arcaine and diethylenetriamine do not inhibit spermidine enhancement of [ 3 H]CPP binding. Mg 2+ also does not compete with the spermidine enhancement of [ 3 H]CPP binding. Ifenprodil inhibits the spermidine enhancement of [ 3 H]CPP binding. The data suggest two or more polyamine sites, with arcaine selective for the site that enhances [ 3 H]TCP binding. Neomycin is an agonist at one polyamine site and an antagonist to the second.