5-HTP induced diarrhea as a carcinoid syndrome model in mice?
Serotonin (5-HT) is present in the gastrointestinal tract and is probably one of the compounds responsible for diarrhea in patients presenting with carcinoid syndrome. Intraperitoneal administration of L-5-hydroxytryptophan (L-5-HTP) at doses of 25 to 100 mg/kg dramatically increase defecation in mice. In this new paradigm, counting fecal boli deposited is simple and the appraised or inhibition of diarrhea induced by ip 25 mg/kg of L-5-HIP is very clear, with a good reproducibility of scores. L-5-HTP needs to be metabolized into 5-HT to be active; benserazide, an inhibitor of decarboxylase, antagonized the diarrhea induced by 5-HT. Among the 5-HT antagonists used in interaction with 5-HT, only these of the 5-HT3 type (ondansetron, granisetron, tropisetron) and, to a lesser extent 5-HT2 type (ritanserin), decreased the diarrhea induced by 5-HTP. The 5-HT4 receptor agonists from the benzamide family (metoclopramide and zacopride) increased defecation in mice but the effect failed to reach statistical significance.
Bourin
M
M
GIS Medicament, Faculty of Medicine, Nantes, France.
Hascoet
M
M
Deguiral
P
P
D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D002276:Carcinoid Tumor / Q000139:chemically induced; D003672:Defecation / Q000187:drug effects*; D003967:Diarrhea / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D001545:Benserazide; D006916:5-Hydroxytryptophan