The involvement of 5-HT3 and 5-HT4 receptors in two models of gastrointestinal transit in mice.
Our aim was to study the involvement of 5-hydroxytryptamine (5-HT)(3) and 5-HT(4) receptors in two models of gastrointestinal transit (GIT) in mice: the 5-hydroxytryptophan (5-HTP)-induced diarrhea and intestinal inflammation produced by an irritant agent, croton oil (CO). 5-HTP (10 mg/kg) produced diarrhea that was significantly inhibited after pretreatment with ondansetron (5-HT(3) antagonist) or RS 39604 (5-HT(4) antagonist) (1-5 mg/kg). The GIT speed was increased after CO and 5-HTP administration. 5-HT(3-4) antagonists decreased GIT after 5-HTP-treatment but not after CO-treatment. Our results show that 5-HT(3) and 5-HT(4) receptors are involved in 5-HTP-induced diarrhea. This may be the reason why 5-HT(3-4) antagonists could be useful in the treatment of carcinoid syndrome diarrhea. 5-HT(3-4) antagonists were not effective in the modifications of GIT; nevertheless, they could be useful in the treatment of inflammatory bowel diseases because some symptoms as abdominal pain, discomfort or abnormal bowel function are modulated via 5-HT(3).
Pascual
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D
Unidad de Farmacología, Departamento Ciencias de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain.
Alsasua
A
A
Goicoechea
C
C
Martín
M I
MI
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology; D003436:Croton Oil / Q000494:pharmacology; D003879:Dermatologic Agents / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy*; D005772:Gastrointestinal Transit / Q000502:physiology*; D007422:Intestines / Q000187:drug effects*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D000930:Antidiarrheals; D003879:Dermatologic Agents; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D017294:Ondansetron; D009020:Morphine; D003436:Croton Oil; D006916:5-Hydroxytryptophan