EFFECTS OF NITROPRUSSIDE AND REDOX REAGENTS ON NMDA RECEPTORS EXPRESSED IN XENOPUS-OOCYTES

We have examined the effects of oxidizing and reducing agents and sodi um nitroprusside (SNP) on currents evoked by NMDA (N-methyl-D-aspartat e) using the Xenopus oocyte expression system. Oocytes were injected w ith RNA prepared from either whole rat brain or from the NMDAR1 clone recently isolated from rat brain. Bath application of 1-1000 mu M SNP, which releases nitric oxide and ferrocyanide, caused a rapid inhibiti on of NMDA-evoked current in both preparations. The inhibitory effect reversed spontaneously within 15 min. Kainate responses were not affec ted by SNP. Exposure to the reducing agent, dithiothreitol (DTT), enha nced NMDA currents; the oxidant, 5,5-dithio-bis-2-nitrobenzoic acid (D TNB), inhibited NMDA responses, as has been observed in other preparat ions. The site of action of SNP appeared to be different than the DTT/ DTNB redox site for several reasons: SNP and DTNB inhibitions were add itive at high doses, DTT did not rapidly reverse SNP effects, and SNP and DTT treatments did not show the same susceptibility to block by th e NMDA antagonist, aminophosphonovaleric acid (APV). The results demon strate that modulation of NDMA receptors by SNP is a property of homom eric channels and is retainedg when the NMDAR1 subunit is expressed in oocytes.