A nonneuronal 5-hydroxytryptamine receptor 3 induces chloride secretion in the rat distal colonic mucosa

• Published in: The American journal of surgery Vol. 190; no. 5; pp. 736 - 738
• Main Authors: Day, Jarrod, King, Brian, Haque, Sheikh M., Kellum, John M.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2005; Elsevier; Elsevier Limited
• Subjects: 5-hydroxytryptamine receptor 3; Analysis of Variance; Animals; Biological and medical sciences; Chlorides - metabolism; Cholera; Colon; Colon - cytology; Colon - innervation; Colon - metabolism; General aspects; In Vitro Techniques; Indoles - pharmacology; Intestinal Mucosa - drug effects; Intestinal Mucosa - innervation; Intestinal Mucosa - secretion; Intestinal secretion; Ion Transport - drug effects; Ion Transport - physiology; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Ondansetron - pharmacology; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, Serotonin, 5-HT3 - drug effects; Receptors, Serotonin, 5-HT3 - metabolism; Rodents; Serotonin; Serotonin - analogs & derivatives; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Tetrodotoxin - pharmacology; Serotonin; 5-hydroxytryptamine receptor 3; Intestinal secretion; Rat; Secretion; Mucosa; Rodentia; Gut; Medicine; Vertebrata; Mammalia; Treatment; Animal; Surgery; Chlorides; Distal; Neurotransmitter; Colon; Biological receptor
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2005.07.012

The 5-HT 3 receptor is a serotonin receptor believed to reside on enteric neurons. However, several studies belie an exclusive neural localization. Our hypothesis is that the 5-HT 3 receptor agonist, 2-methyl-5-HT (2Me5HT), induces chloride secretion despite neural blockade, which can be blocked by a 5-HT 3 receptor antagonist. Rat distal colon was stripped of its muscularis, mounted as mucosal sheets in Ussing chambers, and short-circuited. Adjacent sheets were pretreated with 1 μmol/L of the neurotoxin, tetrodotoxin, and incubated with 2Me5HT (50 μmol/L) alone or with a 5-HT 3 (0.3 μmol/L ondansetron or 0.3 μmol/L tropisetron) or a 5-HT 4 (0.3 μmol/L GR11808) receptor antagonist. Short-circuit current ( I sc ) was measured continuously. 2Me5HT caused an increase in I sc , which was significantly ( P <.01, repeated measures analysis of variance) inhibited by ondansetron (n = 8) and tropisetron (n = 5) but not by GR11808. A 5-HT 3 receptor is present at the mucosal level that mediates chloride secretion by a nonneural pathway.