Proline-glutamate interactions in the CNS.

1. Crude synaptosomes (P2) and synaptosomal membranes were prepared from normal C57/B110 mouse brains and Wistar rats respectively. 2. [3H]Pro binding to mouse brain synaptic membranes was examined in the presence of competitive NMDA antagonist, MK-801, or HA-966. Conversely, the effects of l-proline on [3H]MK-801 binding were also probed. The effects of l-proline on glutamate-medicated [Ca+2]i levels were tested. 3. The authors could not detect any effect of proline on glutamate-mediated [CA+2]i levels using FURA-2 in synaptosomes or neuroblastoma cells. 4. NMDA competitive antagonists, AP-7, CPP, and CGS 19755 inhibit [3H]Pro binding to mouse brain synaptic membranes. 5. MK-801, a NMDA channel blocker, also inhibits [3H]Pro binding, but 200 mM proline is incapable of inhibiting [3H]MK-801 binding. 6. HA-966, a glycine site partial agonist inhibits [3H]Pro binding. Proline has modest effects on [3H]glycine binding.