The role of serotonin in the pathophysiology of irritable bowel syndrome

Coordinated activities of the central, autonomic, and enteric nervous systems modulate intestinal motor, sensory, and secretory activities that may contribute to the triad of dysfunction (altered motility, altered sensation, and psychosocial distress) observed in patients with irritable bowel syndrome (IBS). Autonomic modulation of gastrointestinal (GI) function occurs via the actions of neurotransmitters and neuromodulators such as serotonin (5-hydroxytryptamine, or 5-HT), norepinephrine, and dopamine. Of those modulators, serotonin has received the most attention with respect to disorders of GI function. Serotonin exerts its effects via neurocrine, paracrine, and endocrine pathways. Recent studies have demonstrated that serotonin, acting primarily through 5-HT₃ and 5-HT₄ receptors, is intricately involved in initiating the peristaltic reflex and facilitating intraluminal secretions. Serotonin receptors mediate reflex control of GI motility and secretion and may influence the perception of bowel function and pain under some circumstances. GI motor activity and sensory dysfunction in patients with IBS may be a result of alterations in serotonin levels or associated 5-HT receptors. Serotonin agonists and antagonists such as tegaserod, a 5-HT₄ agonist, may offer new treatments that normalize GI motor and sensory functions in patients with disorders of GI function.