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Intracolonic glycerol induces abdominal contractions in rats: Role of 5‐HT 3 receptors
Author(s) -
Botella A,
Fioramonti J,
Eeckhout C,
Bueno L
Publication year - 1998
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1998.tb00995.x
Subject(s) - granisetron , nociception , saline , anesthesia , ondansetron , 5 ht3 receptor , medicine , pharmacology , serotonin , reflex , 5 ht receptor , receptor , chemistry , antiemetic , nausea , vomiting
Summary— Serotonin and 5‐HT 3 receptors may be involved in the activation of nociceptive afferent pathways by rectal distension. In rats, intracolonic infusion of glycerol is able to trigger nociceptive inputs as evidenced by the occurrence of abdominal constrictions. This work was designed to evaluate the influence of 5‐HT 3 receptor antagonists on this reflex and to approach the site of action by comparing their relative efficacies according to the route of administration. Male Wistar rats (250–350 g) were surgically prepared for abdominal electromyography and a catheter was placed in the colonic lumen. Five days after surgery, electrical activity of abdominal muscles was recorded before and during (20 min) intracolonic infusion of glycerol (60% glycerol + 40% saline, rate 0.75 mL/h). Cilansetron was administered intraperitoneally, 15 min before glycerol infusion, at doses of 5 to 500 μg/kg. Granisetron, ondansetron and cilansetron were administred at the dose of 20 μg/kg by intraperitoneal (ip), intravenous (iv) or intracolonic (ic) routes. The number of abdominal spike bursts was used as an index of visceral nociception. Intracolonic infusion of glycerol increased significantly ( P < 0.05) the number of abdominal spike bursts during the time of infusion compared with saline (30.6 ± 6.6 vs 4.5 ± 3.4 bursts). When administered ip, cilansetron dose‐dependently reduced the frequency of abdominal spike bursts from the dose of 20 μg/kg ip. Administration ip of granisetron and ondansetron at this dose also significantly reduced the number of abdominal spikes (19.0 ± 6.0 and 18.3 ± 6.9 respectively). Cilansetron, ondansetron and granisetron were also effective by iv and ic routes, cilansetron was more active by the ic route. Serotonin, via 5‐HT 3 receptors, is involved in the mediation of abdominal contractions induced by intracolonic infusion of glycerol. 5‐HT 3 receptor antagonists are also active by ic route suggesting a local site of action.