Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport.
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.
Sayer
Brooke
B
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada.
Lu
Jun
J
Green
Christina
C
Söderholm
Johan D
JD
Akhtar
Mahmood
M
McKay
Derek M
DM
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
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