Substance P receptor desensitization in the dorsal horn: possible involvement of receptor-G protein complexes

Abstract

The repeated administration of a high dose of substance P (SP) onto the spinal cord has been shown to attenuate behavioral response to an intense heat (tail-flick) or noxious mechanical stimulus (paw pressure). Studies performed to investigate the action of spinal SP have suggested that changes in behavioral responses involve endogenous opiate or neurokinin systems. This study was performed to investigate whether the binding characteristics of SP receptors in the dorsal horn are altered following successive administration of SP. Two populations of [ 3H]-SP binding sites were distinguished on the basis of their binding affinity. Gpp(NH)p, a stable analogue of GTP, decreased the size and affinity of the high affinity binding component selectively labelled with [ 125I]-Bolton Hunter-SP. Repeated intratehcal administration of SP (15 μg) which reduced behaviors also reduced the number and affinity binding sites. Thus, attenuated behaviors in response to repeated administration of SP are paralleled by an alteration of SP binding in the dorsal horn. The altered agonist affinity seen under desensitizing conditions raises the possibility that SP receptor desentization involves an uncoupling of receptor-G protein complexes.