5-Hydroxytryptamine (serotonin) in the gastrointestinal tract

Abstract

Purpose of review: Although the gut contains most of the body's 5-hydroxytryptamine (5-HT), many of its most important functions have recently been discovered. This review summarizes and directs attention to this new burst of knowledge.

Recent findings: Enteroendocrine cells have classically been regarded as pressure sensors, which secrete 5-HT to initiate peristaltic reflexes; nevertheless, recent data obtained from studies of mice that selectively lack 5-HT either in enterochromaffin cells (deletion of tryptophan hydroxylase 1 knockout; TPH1KO) or neurons (TPH2KO) imply that neuronal 5-HT is more important for constitutive gastrointestinal transit than that of enteroendocrine cells. The enteric nervous system of TPH2KO mice, however, also lacks a full complement of neurons; therefore, it is not clear whether slow transit in TPH2KO animals is due to their neuronal deficiency or absence of serotonergic neurotransmission. Neuronal 5-HT promotes the growth/maintenance of the mucosa as well as neurogenesis. Enteroendocrine cell derived 5-HT is an essential component of the gastrointestinal inflammatory response; thus, deletion of the serotonin transporter increases, whereas TPH1KO decreases the severity of intestinal inflammation. Enteroendocrine cell derived 5-HT, moreover, is also a hormone, which inhibits osteoblast proliferation and promotes hepatic regeneration.

Summary: New studies show that enteric 5-HT is a polyfunctional signalling molecule, acting both in developing and mature animals as a neurotransmitter paracrine factor, endocrine hormone and growth factor.