Cellular and subcellular localization of neurokinin-1 and neurokinin-3 receptors in primate globus pallidus.

The primate globus pallidus receives massive innervations from GABAergic striatal neurons that co-release the neuropeptide substance P (SP). To expand our knowledge regarding SP interaction at pallidal level, we used single and double antigen retrieval methods to study the cellular and subcellular localization of SP and its high-affinity receptors neurokinin-1 (NK-1R) and neurokinin-3 (NK-3R) in the globus pallidus of the squirrel monkey (Saimiri sciureus). At the light microscopic level, a large number of neurons and fibers located in both the external (GPe) and internal (GPi) segments of the globus pallidus expressed NK-1R or NK-3R immunoreactivity. At the electron microscopic level, both NK-1R and NK-3R were mainly associated with intracellular sites or located at extrasynaptic positions on the plasma membrane. Presynaptic axon terminals forming symmetric and asymmetric synapses occasionally contained NK-1R and NK-3R. Neurokinin receptors were also observed in a proportion of SP-immunoreactive axon terminals, but these terminals preferentially expressed NK-3R. The pattern of distribution of NK-1R and NK-3R in GPe and GPi indicates that SP effects at pallidal level are mediated through postsynaptic receptor as well as presynaptic autoreceptors and heteroreceptors. These morphological data suggest that, either alone or in conjunction with GABA, SP could have a wide range of effects at pallidal level. This neuroactive peptide may influence in a significant manner the integration and treatment of neural information that flows through the basal ganglia.