title: Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport.
abstract: 1. Neuronal cholinergic input is an important regulator of epithelial electrolyte transport and hence water movement in the gut. 2. In this study, colitis was induced by treating mice with 4% (w v(-1)) dextran sodium-sulphate (DSS)-water for 5 days followed by 3 days of normal water. Mid-colonic segments were mounted in Ussing chambers and short-circuit current (Isc, indicates net ion movement) responses to the cholinergic agonist, carbachol (CCh; 10(-4) M)+/-tetrodotoxin, atropine (ATR), hexamethonium (HEX), naloxone or phenoxybenzamine were assessed. 3. Tissues from mice with DSS-induced colitis displayed a drop in Isc in response to CCh (-11.3+/-3.3 microA/cm(2)), while those from control mice showed a transient increase in Isc (76.3+/-13.0 microA/cm(2)). The DeltaIsc in colon from DSS-treated mice was tetrodotoxin-sensitive, atropine-insensitive and was reversed by hexamethonium (HEX+CCh=16.7+/-7.8 microA/cm(2)), indicating involvement of a nicotinic receptor. 4. CCh induced a drop in Isc in tissues from controls only when they were pretreated with the cholinergic muscarinic receptor blocker, atropine: ATR+CCh=-21.3+/-7.0 microA/cm(2). Nicotine elicited a drop in Isc in Ussing-chambered colon from both control and DSS-treated mice that was TTX-sensitive. 5. The drop in Isc evoked by CCh challenge of colonic tissue from DSS-treated mice or ATR+CCh challenge of control tissue was not significantly affected by blockade of opiate or alpha-adrenergic receptors by naloxone or phenoxybenzamine, respectively. 6. The data indicate that DSS-colitis reveals a nicotinic receptor that becomes important in cholinergic regulation of ion transport.
authors.affiliation: Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Brooke
authors.initials: B
authors.lastname: Sayer
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Christina
authors.initials: C
authors.lastname: Green
authors.forename: Johan D
authors.initials: JD
authors.lastname: Söderholm
authors.forename: Mahmood
authors.initials: M
authors.lastname: Akhtar
authors.forename: Derek M
authors.initials: DM
authors.lastname: McKay
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D018738:Hexamethonium / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009294:Narcotics / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D009294:Narcotics; D011942:Receptors, Adrenergic, alpha; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D018738:Hexamethonium; D013779:Tetrodotoxin; D009538:Nicotine; D001285:Atropine; D002217:Carbachol; D016264:Dextran Sulfate