Substance P modulates glutamate-induced currents in acutely isolated rat spinal dorsal horn neurones

The whole-cell patch-clamp technique was used to examine the effect of substance P (SP) on glutamate-induced currents in freshly dissociated rat spinal dorsal horn neurons (LI-III). In 48% of examined cells SP (10 −10–10 −6 M) at −70 mV, induced an inward current that desensitized in the continued presence of SP. When applied simultaneously with, or prior to l-glutamate, SP caused a potentiation of l-glutamate-induced current in 65% of the tested cells. Since glutamate activates both N- methyl- d-aspartate (NMDA) and non-NMDA receptors in rat dorsal horn neurons, selective agonists, kainate, quisqualate, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and NMDA were used to determine which subtype of excitatory amino acid receptors interacted with SP. We found that the responses to quisqualate, kainate, and AMPA were not significantly affected by SP (< 20% increase). In contrast, the inward currents induced by NMDA (30–300 μM) appear to be reduced and potentiated after the administration of 2–200 nM of SP. These results suggest that post-synaptic mechanisms of action of tachykinins may contribute to the regulation of the strength of glutamate-mediated excitatory transmission in the rat spinal dorsal horn.