CELLULAR-LOCALIZATION AND DISTRIBUTION OF THE CLONED MU-OPIOID AND KAPPA-OPIOID RECEPTORS IN RAT GASTROINTESTINAL-TRACT

Several pharmacological and electrophysiological studies have shown th at the opioid receptors are widely distributed in the gastrointestinal tract. Despite such consensus, there are conflicting findings regardi ng their effects in intestinal function, and their precise site of act ion remained unclear. The aim of the present study was therefore to de lineate the cellular localization of mu and kappa opioid receptors in rat gastrointestinal tract using polyclonal antibodies generated to C- terminal end of the cloned mu (63 amino acids) and kappa (41 amino aci ds) receptors. The distribution of mu differs from that of kappa recep tors within the gastrointestinal wall, with a greater abundance of mu receptor-like immunoreactive fibres in all intestinal layers. Numerous neurons expressing mu receptor-like proteins were found in the submuc osal plexus with comparatively few in the myenteric plexus. In contras t, a higher number of neurons expressing kappa receptor-like immunorea ctivity were visualized in the myenteric plexus with a small number in the submucosal plexus. A high number of immunopositive neurons were f ound in the myenteric plexus of the stomach and the proximal colon wit h both antibodies. In the submucosal and mucosal layers, mu receptor-i mmunoreactive fibres were more abundant and distributed around the cry pts, blood vessels and lymphatic nodes. Interestingly, numerous mu and fewer kappa receptor-immunoreactive interstitial cells are localized in the region of myenteric plexus and at the internal border of the ci rcular muscle. Finally, smooth muscle cells did not demonstrate any mu - nor kappa-receptor immunoreactivity. These findings suggest that in the rat gastrointestinal tract, mu and kappa opioid receptors may dire ctly influence neuronal and interstitial cell activity. This appears n ot to be the case for the smooth muscle cells. In the muscular layers, the anatomical data point to mu receptor actions being mediated by ne rve terminals, whereas kappa-receptor effects may be mediated by both nerve terminals and somatodendritic synaptic mechanisms. In contrast, in the submucosal and mucosal layers, mu receptors predominate and are localized on both nerve terminals and somatodendritic synaptic elemen ts. (C) 1997 IBRO. Published by Elsevier Science Ltd.