CELLULAR SITES OF EXPRESSION OF THE NEUROKININ-1 RECEPTOR IN THE RAT GASTROINTESTINAL-TRACT

In the digestive system, substance P is an excitatory transmitter to m uscle, a putative excitatory neuro-neuronal transmitter, a vasodilator , and a mediator in inflammatory processes. Many of the biological eff ects of substance P are mediated by a high-affinity interaction with t he tachykinin receptor neurokinin-1. The aim of the present study was to identify the sites of expression of this receptor in the rat stomac h and intestine by immunohistochemistry with a polyclonal antiserum ra ised to the intracellular C-terminal portion of the rat neurokinin-1 r eceptor. Neurokinin-1 receptor immunoreactivity is present in a large population of enteric neurons. The relative density of these neurons a long the gut is colon > ileum >> stomach. In the intestine, stained ne urons have a smooth cell body with processes that can be followed with in and between plexuses, and make close approaches to other neuronal c ells, but do not appear to project outside the plexuses, suggesting th at they are interneurons. In the stomach, neurokinin-1 receptor-immuno reactive neurons are infrequent and have a poorly defined and irregula r shape. Neurokinin-1 receptor immunoreactivity is also localized to n umerous non-neuronal cells in the inner portion of the circular muscle layer of the small intestine, which have the appearance of small dark smooth muscle cells or interstitial cells of Cajal. These cells are p ostulated to form a ''stretch-sensitive'' system with the deep muscula r plexus and thus constitute an important site of regulation of muscle activity. Double labeling immunofluorescence was used to simultaneous ly localize neurokinin-1 receptor and substance P/tachykinin immunorea ctivities. These experiments demonstrate that in the enteric plexuses, substance P/tachykinin-immunoreactive varicose fibers encircle the ce ll bodies of most neurokinin-1 receptor-containing neurons, and in the inner portion of the circular muscle layer of the small intestine the y lie close to neurokinin-1 receptor-immunoreactive non-neuronal cells . In addition, some enteric neurons express both neurokinin-1 receptor and substance P/tachykinin immunoreactivities. The present study prov ides strong evidence that the neurokinin-1 receptor is the tachykinin receptor mediating the actions of substance P on enteric neurons and s mooth muscle. (C) 1995 Wiley-Liss, Inc.