Relationship between neurokinin-1 receptor and substance P in the striatum: Light and electron microscopic immunohistochemical study in the rat

The synaptic relationship between substance P (SP) and its receptor, i.e., neurokinin-1 receptor (NK1R), was examined in the striatum of the rat by co nfocal laser-scanning microscopy and electron microscopy. For confocal lase r-scanning microscopy, triple-immunofluorescence histochemistry was perform ed to label NK1R, SP, and vesicular acetylcholine transporter (a specific m arker for cholinergic neurons). In electron microscopic double-immunolabeli ng study, immunoreactivity for NK1R was detected with the silver-intensifie d gold method, while immunoreactivity for SP was detected with peroxidase i mmunohistochemistry. Simultaneous immunolabeling of NK1R and SP revealed si gnificant mismatch at the synaptic level: although some SP-immunopositive a xon terminals were in synaptic contact with NK1R-immunopositive sites of pl asma membrane, NK1R-immunoreactivity was observed at both synaptic and non- synaptic sites of plasma membrane. Thus, SP released fi om the sites remote from NK1Rs might diffuse in the extracellular fluid to act, as a paracrine neurotransmitter, on NK1Rs distant from its releasing site. SP neurotransm ission in the striatum might occur not only synaptically but also extrasyna ptically. The SP-NK1R system might constitute an association system within the striatum. (C) 2000 Wiley-Liss, Inc.