5-HTP induced diarrhea as a carcinoid syndrome model in mice?

Fundam Clin Pharmacol. 1996;10(5):450-7. doi: 10.1111/j.1472-8206.1996.tb00600.x.

Abstract

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.

MeSH terms

  • 5-Hydroxytryptophan / administration & dosage
  • 5-Hydroxytryptophan / metabolism
  • 5-Hydroxytryptophan / toxicity*
  • Animals
  • Benserazide / pharmacology
  • Carcinoid Tumor / chemically induced
  • Defecation / drug effects*
  • Diarrhea / chemically induced*
  • Diarrhea / drug therapy
  • Diarrhea / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Serotonin / metabolism
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology*
  • Stereoisomerism

Substances

  • Enzyme Inhibitors
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • Benserazide
  • 5-Hydroxytryptophan