SUBSTANCE-P POST-SYNAPTICALLY POTENTIATES GLUTAMATE-INDUCED CURRENTS IN DORSAL VAGAL NEURONS

We examined the post-synaptic actions of glutamate, N-methyl-D-asparta te (NMDA) and substance P on dorsal vagal neurons, using the patch-cla mp technique on brainstem slices of young rats. The vagal neurons were identified electrically and histologically. All vagal neurons respond ed to glutamate and NDMA and about 30% to substance P, with dose-depen dent inward currents. The glutamate-induced currents were blocked part ially by either CPP 3((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) or CNQX (6-cyano-7-nitro-quinoxaline-2,3-dione), indicating tha t these currents resulted from the activation of at least two types of glutamate receptors: NMDA receptors and AMPA/kainate receptors. The N K1 receptor-selective antagonist, RP67580, blocked substance P-induced currents, suggesting that NK1 receptors do coexist with NMDA receptor s and AMPA/Kainate receptors. Substance P potentiated the effects of g lutamate. This potentiation lasted 10-20 min and was blocked by CPP an d by RP67580, but not by CNQX, demonstrating that the increase in glut amate-induced currents resulted from the interaction between NK1 recep tors and NMDA channels. These results provided the first evidence that the receptors for substance P and glutamate coexist on dorsal vagal n eurons and interact with each other to modulate visceral efferent func tions. (C) 1998 Elsevier Science B.V. All rights reserved.