Substance P post-synaptically potentiates glutamate-induced currents in dorsal vagal neurons

We examined the post-synaptic actions of glutamate, N-methyl-D-aspartate (NMDA) and substance P on dorsal vagal neurons, using the patch-clamp technique on brainstem slices of young rats. The vagal neurons were identified electrically and histologically. All vagal neurons responded to glutamate and NDMA and about 30% to substance P, with dose-dependent inward currents. The glutamate-induced currents were blocked partially by either CPP (3((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) or CNQX (6-cyano-7-nitro-quinoxaline-2,3-dione), indicating that these currents resulted from the activation of at least two types of glutamate receptors: NMDA receptors and AMPA/kainate receptors. The NK1 receptor-selective antagonist, RP67580, blocked substance P-induced currents, suggesting that NK1 receptors do coexist with NMDA receptors and AMPA/Kainate receptors. Substance P potentiated the effects of glutamate. This potentiation lasted 10-20 min and was blocked by CPP and by RP67580, but not by CNQX, demonstrating that the increase in glutamate-induced currents resulted from the interaction between NK1 receptors and NMDA channels. These results provided the first evidence that the receptors for substance P and glutamate coexist on dorsal vagal neurons and interact with each other to modulate visceral efferent functions.