Effects of RP 67580 on substance P-elicited responses and postsynaptic potentials of motoneurones of the rat isolated spinal cord.

The effect of RP 67580, a recently developed antagonist selective for the NK1 tachykinin receptors of peripheral tissues, was studied with intracellular recording from motoneurones of the rat isolated spinal cord. In the presence of RP 67580 (1-2 microM), membrane depolarization induced by the putative transmitter substance P (SP) was either unchanged or enhanced (an effect prevented by tetrodotoxin; TTX). Neither short nor long excitatory synaptic potentials (EPSPs) were antagonized by RP 67580. Sustained synaptically evoked depolarizations (mimicking noxious stimuli and thus presumed to be at least partly mediated by SP) were also insensitive to RP 67580. These data suggest the existence of a pharmacologically distinct NK1 receptor population insensitive to RP 67580) in the neonatal rat spinal cord.