Presynaptic and postsynaptic subcellular localization of substance P receptor immunoreactivity in the neostriatum of the rat and rhesus monkey (Macaca mulatta).

The substance P receptor (SPR) gene is expressed at high levels in basal ganglia, but the paucity of information about localization of the encoded receptor protein has limited our understanding of this peptide's involvement in cellular and subcellular mechanisms in this region. Morphological evidence in the rodent striatum indicates that SPRs are expressed in postsynaptic neuronal elements, while pharmacological studies suggest the existence of presynaptic SPRs in this structure. We have examined the issue of subcellular distribution of this receptor protein in rat and primate neostriatal tissue, employing an antiserum raised against SPR. Electron microscopic analysis revealed that SPR immunoreactivity is present in presynaptic and postsynaptic neuronal elements in both species. In agreement with earlier studies, SPR immunoreactivity was found predominantly in perikarya and dendrites of a small subset of striatal neurons, the large and medium-sized aspiny interneurons. In addition, a small but significant proportion of the immunoreaction product was localized in presynaptic profiles, both in axons and axon terminals. The majority of SPR immunoreactive boutons formed asymmetric synapses with dendrites and dendritic spines. The association of SPRs with asymmetric synapses provides a morphological substrate for peptidergic modulation of excitatory neurotransmission of extrastriatal origin. A minor proportion of immunolabeled axons established symmetric synaptic junctions with unlabeled dendrites. The presence of SPRs in these synapses suggests a presynaptic peptidergic modulation of intrinsic striatal transmitter systems. The observations in this study also indicate that SPR mediates a complex combination of postsynaptic and presynaptic effects on acetylcholine release in the mammalian striatum.