Regulation of NMDA-induced [3H]dopamine release from rat hippocampal slices through sigma-1 binding sites.
To examine the interaction between ionotropic glutamate receptors and sigma binding sites, we made use of [3H]dopamine release from rat hippocampal slices. Agonists for ionotropic glutamate receptors such as N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate evoked release of [3H]dopamine from rat hippocampal slices, in a dose-dependent manner. (+)-Pentazocine, a prototype sigma1 agonist, attenuated the NMDA-induced [3H]dopamine release dose-dependently and significantly as did non-competitive NMDA antagonists such as 5-methyl-10,11-dihydro-5H-dibenzo(a,b)cyclohepten-5,10-imine maleate (MK-801) and phencyclidine. In contrast, (+)-pentazocine had no effect on AMPA- or on kainate-induced [3H]dopamine release. Sigma-1 receptor antagonists including N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl] ethylamine monohydrochloride (NE-100), 1(cyclopropylmethyl)-4-(2'-(4"-fluorophenyl)-2'-oxoethylpiperidine (DuP734) and 1-(cyclopropylmethyl)-4-(2',4"-cianophenyl)-2'-oxoethyl)-pip eridine hydrobromide (XJ448) prevented significantly the inhibitory effect of (+)-pentazocine on NMDA-induced [3H]dopamine release, without affecting the release of [3H]dopamine evoked by NMDA. The inhibitory effect of (+)-pentazocine on [3H]dopamine release was preserved even in the presence of tetrodotoxin. These results suggest that sigma1 binding sites selectively interact with the NMDA receptor channel complex among ionotropic glutamate receptors, and that sigma1 binding sites may be involved in modulating the release of dopamine in the rat hippocampus by interacting with the NMDA receptor on dopaminergic nerve terminal.
1st Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd, Ohmiya, Saitama, Japan. S13555@ccm.taisho.co.jp
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Chaki
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Okuyama
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Ogawa
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Tomisawa
D000818:Animals; D001665:Binding Sites; D004298:Dopamine / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D000097605:Sigma-1 Receptor
D004298:Dopamine; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D016202:N-Methylaspartate; D010423:Pentazocine; D017470:Receptors, Glutamate; D017480:Receptors, sigma; D013779:Tetrodotoxin; D014316:Tritium; D000097605:Sigma-1 Receptor