Solubilization of the NMDA Receptor Ion Channel Complex from Rat Brain

Abstract

Several lines of evidence indicate that N-methyl-D-aspartic acid (NMDA)-sensitive receptors form a macromolecular complex which consists of at least three distinct sites (for example, see review by Robinson and Coyle, 1987); 1) NMDA recognition sites labeled by [3H]glutamic acid (Glu) (Ogita and Yoneda, 1988) or [3H](±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) (Murphy et al., 1987), 2) cation channel sites labeled by radiolabeled noncompetitive NMDA antagonists, (+)-5-methyl-lO, ll-dihydro-5H-dibenzo [a,d] cyclohepten-5 , 10-imine (MK-801) (Foster and Wong, 1987) and N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) (Loo et al., 1986), 3) glycine (Gly) recognition sites labeled by [3H]Gly, which are insensitive to strychnine (GlyB sites) (Ogita et al., 1989). In addition, recent binding studies have raised the possibility that modulatory sites by polyamines may also exist on the NMDA receptor ion channel complex in addition to the aforementioned three sites, which is based on the findings that polyamines, such as spermidine (SPD) and spermine, markedly enhance both [3H]MK-801 and [3H]TCP bindings (Ransom and Stec, 1988) and that the potentiation by SPD is antagonized by some other polyamines, including putrescine and cadaverine (Williams et al., 1989).