The opioid system in the gastrointestinal tract.
Mu-, delta- and kappa-opioid receptors (ORs) mediate the effects of endogenous opioids and opiate drugs. Here we report (1) the distribution of muOR in the guinea-pig and human gastrointestinal tract in relation to endogenous ligands, to functionally distinct structures in the gut and to deltaOR and kappaOR; and (2) the ligand-induced muOR endocytosis in enteric neurones using in vitro and in vivo models. In the guinea pig, muOR immunoreactivity is confined mainly to the myenteric plexus. MuOR myenteric neurones are most numerous in the small intestine, followed by the stomach and the proximal colon. MuOR immunoreactive fibres are dense in the muscle layer and the deep muscular plexus, where they are in close association with interstitial cells of Cajal. This distribution closely matches the pattern of enkephalin. MuOR enteric neurones comprise functionally distinct populations of neurones of the ascending and descending pathways of the peristaltic reflex. In human gut, muOR immunoreactivity is localized to myenteric and submucosal neurones and to immune cells of the lamina propria. DeltaOR immunoreactivity is located in both plexuses where it is predominantly in varicose fibres in the plexuses, muscle and mucosa, whereas kappaOR immunoreactivity appears to be confined to the myenteric plexus and to bundles of fibres in the muscle. MuOR undergoes endocytosis in a concentration-dependent manner, in vitro and in vivo. Pronounced muOR endocytosis is observed in neurones from animals that underwent abdominal surgery that has been shown to induce delay in gastrointestinal transit. We can conclude that all three ORs are localized to the enteric nervous system with differences among species, and that muOR endocytosis can be utilized as a means to visualize enteric neurones activated by opioids and sites of opioid release.
Sternini
C
C
CURE Digestive Diseases Research Center, Division of Digestive Diseases, Departments of Medicine and Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. csternin@ucla.edu
Patierno
S
S
Selmer
I-S
IS
Kirchgessner
A
A
D000328:Adult; D000818:Animals; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000032:analysis* / Q000378:metabolism; D011957:Receptors, Opioid / Q000032:analysis* / Q000096:biosynthesis
D009294:Narcotics; D011957:Receptors, Opioid