title: Antisecretory effects of neuropeptide Y in the mouse colon are region-specific and are lost in DSS-induced colitis.
abstract: Regulation of water movement in the gut is an important homeostatic event that is critical to normal intestinal function. We assessed the effect of neuropeptide Y (NPY) on epithelial ion transport in the normal and inflamed mouse colons. Colitis was induced by dextran sodium sulfate (DSS, 4% wt./vol.) administered in the drinking water for 5 days followed by 3 days of regular water. Segments of proximal and distal colons were excised and short-circuit current (I(SC)) was measured in Ussing chambers to assess net electrogenic active ion transport. NPY Y(1) receptor (Y(1)R) expression was measured by quantitative real-time PCR and immunohistochemistry. Challenge of distal colon from normal mice with NPY (10(-7)M) evoked a drop in I(SC) (51.4±9.1 μA/cm(2)), which was dependent on Cl(-) flux, was insensitive to neural blockade with tetrodotoxin and was mediated primarily through the Y(1)R. In contrast, the proximal colon was largely unresponsive to NPY, expressing ~ten-fold less Y(1)R mRNA compared to the distal colon. These findings confirm that specific regional regulation of ion transport occurs in the colon. Segments of proximal and distal colons from mice with DDS-induced colitis were virtually unresponsive to NPY, expressed less Y(1)R mRNA than tissues from control mice and displayed loss of Y(1)R protein expression in the colonic epithelium. This hypo-responsiveness to an antisecretory stimulus adds to the well-documented loss of responsiveness to pro-secretory agents during inflammation, attesting to a profound loss of control of active ion transport during enteric inflammatory disease.
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Klompus
authors.forename: Winnie
authors.initials: W
authors.lastname: Ho
authors.forename: Keith A
authors.initials: KA
authors.lastname: Sharkey
authors.forename: Derek M
authors.initials: DM
authors.lastname: McKay
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity*; D007150:Immunohistochemistry; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000494:pharmacology*; D016133:Polymerase Chain Reaction
chemical_list: D009478:Neuropeptide Y; D016264:Dextran Sulfate