Serotonin in the gastrointestinal tract

Abstract

Purpose of review: To assess the role of serotonin and its control in the manifestations and treatment of lower functional gastrointestinal disorders.

Recent findings: Recent literature has explored several novel concepts in the association of serotonin and symptoms, alterations in tissue levels of serotonin and its reuptake protein, aspects of the genetic determinants of serotonergic function (particularly 5-HTTLPR) and its relationship to gastrointestinal motor and sensory functions, and novel serotonergic agents used in therapy of lower functional gastrointestinal disorders. The most consistent findings are the increase in plasma 5-hydroxytryptamine (5-HT) in diarrheal diseases and reduction in constipation. The serotonin transporter in platelets has an impact on the circulating level of 5-HT. Meta-analysis shows that 5-HTTLPR genotype is not significantly associated with irritable bowel syndrome in Whites or Asians. New 5-HT3 antagonists and 5-HT4 agonists are efficacious and promise to provide relief for patients if they can pass regulatory hurdles.

Summary: Although the most relevant implication for clinical practice remains the evidence that serotonergic agents are efficacious in the treatment of chronic constipation, chronic diarrhea and irritable bowel syndrome, the role of genetic control of 5-HT and its receptors is the subject of ongoing research, and is likely to enhance understanding of the mechanisms and treatment of these diseases.

Figure 1

Profiles of 5-hydroxytryptamine (5-HT) (A) and 5-hydroxyindoleacetic acid (5-HIAA) (B) concentrations and ratio of 5-HIAA:5-HT (C) with respect to meal ingestion (t = 0) in patients with constipation(■)- and diarrhea(•)-predominant IBS and healthy controls (Δ). Data are geometric mean and 95% confidence interval. Reproduced from ref. , Atkinson W, et al. Gastroenterology 2006;130:34–43.

Figure 2

Effect of prucalopride on the proportion of patients having an average of three or more spontaneous, complete bowel movements (SCBMs) per week. Reproduced from ref. , Camilleri M, et al. N Engl J Med 2008;358:2344–2354.