期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 135, 期 7, 页码 1794-1800出版社
WILEY
DOI: 10.1038/sj.bjp.0704633
关键词
mouse; colon; nervous system; short-circuit current; muscarinic; nicotinic; inflammation
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 Ise in response to CCh -11.3 +/- 3.3 muA/cm(2)), while those from control mice showed a transient increase in Ise (76.3 +/- 13.0 muA/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 muA/cm(2)), indicating involvement of a nicotinic receptor. 4 CCh induced a drop in Ise in tissues from controls only when they were pretreated with the cholinergic muscarinic receptor blocker, atropine: ATR + CCh = -21.3 +/- 7.0 muA/cm(3). Nicotine elicited a drop in Ise in Ussing-chambered colon from both control and DSS-treated mice that was TTX-sensitive. 5 The drop in Ise 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. British Journal of Pharmacology.
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