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Modulation of Endomorphin-2 to Neurogenic Mucosal Secretion in Human Colon
Jinping Gao1, 2, Chenglong LI1, Dengping Shi1, Weiguo Dong3, Kaixiu Wang1, Yuxing Zhang1, Bing Hu1, Hong Xia3, Xi-Yu Wang4, Guo-Du Wang*4

1Surgery, The second people, Jingmen, China; 2Department of Surgery, Hubei Jingchu Technikon Center Hospitol, Jinmen, China; 3Gastroenterology, Hubei province hospital, Wuhan, China; 4Physiology and Cell Biology, OSU, Columbus, OH

Background & Aims: There were inconsistent evidences on functional expression of opioid receptor subtypes and endogenous opioids in gastrointestinal tract (GI) of human and other species. Therefore, it has remained controversy and unclear that endogenous opioids, such as endomorphin-2, mediated receptor subtypes and functional regulation in the GI. The aim of present study addressed the neurochemical phenotypes of endomorphin-2 (EM2) in enteric plexuses and effects of EM2 in human colonic secretion. Methods: Immunofluorescent staining was used to reveal EM2 expression in human colon. Classic Ussing chamber method were employed to detect the colonic mucosal secretion. The human colonic specimens were obtained from 12 adult patients (7 men and 5 women) undergoing intestinal surgery. Results: Immunohistochemistry exhibited that EM2 were expressed in 237 of 489 submucosal neurons of the colonic cryostat sections. Bath application of EM2 (2 mM) in serosal compartment suppressed basic secretion and electrical filed stimulation (EFS)-evoked short circuit current, Cl- secretion in 24 of 24 human colonic preparations. The inhibitory effects of EM2 can be prevented by pretreatment of 5 mM β-FNA, a µ opioid receptor antagonist, or suppressed by preincubation of 1mM MRS2500, a P2Y1 purinergic receptor antagonist in the preparations. NG-Nitro-L-arginine Methyl Ether (L-NAME, 300 mM, n=12), vasoactive intestinal peptide (VIP 6-28, 0.5 mM, n=8), ICI174864, a δ-opioid receptor antagonist (10 mM, n=8) and GNTI (10 mM, n=8) have not markedly affects in EM2-elicited inhibition of the mucosal secretion. EM2 had not inhibited carbachol (2mM) and MRS2365 (2mM) induced increase of the secretion in presence of tetrodotoxin (TTX, 1mM) in 8 of 8 colonic preparations. Conclusions: EM2 functionally expressed in submucosal neurons in human colon. EM2 can activate presynaptic m-opioid receptor to suppress excitatory neurotransmitter, as acetylcholinergic and purinergic signaling molecules, release to modulate colonic neurogenic mucosal secretion. (Supported by The research and development fundings of Jingmen city government,Hubei,China. 2013)


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