NMDA Receptors with Different Sensitivities to Magnesium and Ifenprodil Control the Release of [¹⁴C]Acetylcholine and [³H]Spermidine from Rat Striatal Slices in Vitro

Abstract

KCl (20-100 mM) and N-methyl-D-aspartate (NMDA, 100-1,000 microM) produce concomitant concentration-dependent increases in the release of previously captured [14C]acetylcholine and [3H]spermidine from rat striatal slices in vitro. The effects of NMDA (300 microM) on striatal [14C]acetylcholine and [3H]spermidine release were blocked with equal potencies by the competitive NMDA antagonist CGP 37849, the glycine site antagonist L-689,560, and the NMDA channel blocker dizocilpine. In contrast, although NMDA-evoked [14C]acetylcholine release was antagonized by ifenprodil (IC50 = 5.3 microM) and MgCl2 (IC50 = 200 microM), neither compound antagonized the NMDA-evoked release of [3H]spermidine at concentrations up to 100 microM (ifenprodil) or 1 mM (MgCl2). Distinct NMDA receptor subtypes with different sensitivities to magnesium and ifenprodil therefore exist in the rat striatum.