Serotonin receptors and their role in the pathophysiology and therapy of irritable bowel syndrome

Abstract

Altered 5-HT signaling in the central nervous system and in the gut contributes to hypersensitivity in IBS. The therapeutic effects of 5-HT agonists/antagonists in IBS are likely to be due also to the ability to modulate visceral nociception in the central stress circuits. Further studies are needed in order to develop an optimal treatment.

Neuroendocrine Dysregulation in Irritable Bowel Syndrome Patients: A Pilot Study

“…Indeed, via the gut-brain axis, local 5-HT secretion contributes to central pain perception, visceral hypersensitivity, and transit modification of the GI motility pattern; however, several studies demonstrated alterations in plasma 5-HT in a specific subgroup of IBS patients but not in all IBS patients. 5,6,26 In this study, the mean levels of plasma cortisol were not significantly different between IBS patients and controls, suggesting an uncoupling between the HPA and ANS axes. Our data are consistent with a previous study by Fukudo et al 27 that observed increased plasma levels of adrenocorticotropic hormone but normal levels of cortisol in response to corticotropin releasing hormone injection in IBS patients.…”

“…The pathophysiology of IBS is still unclear, but certainly, it involves a dysregulation of the brain-gut axis. [3][4][5][6] It has been clearly demonstrated that IBS patients show an increased reactivity to psychosocial stressors, with subsequent hypersensitivity leading to distension and abnormal motor pattern of the intestine. 3,7 Approximately 60% of patients with IBS have concomitant mood and anxiety disorders; conversely, 75% of patients with major depression and panic disorder report some IBS symptoms.…”

“…4 Another mediator in both the CNS and peripheral tissues is serotonin (5-hydroxytryptamine, 5-HT), which acts through its interaction with specific receptors. 6 In the gastrointestinal (GI) tract, 5-HT regulates sensory, secretory, and motor functions through the intrinsic and extrinsic nervous system. In particular, in a previous study, 5 we observed that IBS patients showed a significant association between specific psychological characteristics and neuroendocrine markers, especially plasma cortisol and NPY.…”

“…As suggested by Forbes et al 25 in a mouse model, NPY seems to directly inhibit the colonic motor response induced by the corticotrophin-releasing factor receptor activation during stress. Given that the local 5-HT release in the GI tract is involved in excitatory action on vagal afferent fibers and on contraction of smooth colonic muscle, 6 it is possible that indirect high levels of NPY try to maintain normal colonic motor response also during psychological distress, counteracting the effect of 5-HT release. Indeed, via the gut-brain axis, local 5-HT secretion contributes to central pain perception, visceral hypersensitivity, and transit modification of the GI motility pattern; however, several studies demonstrated alterations in plasma 5-HT in a specific subgroup of IBS patients but not in all IBS patients.…”

Роль Вісцеральної Гіперчутливості В Розвитку Синдрому Подразненого Кишечника

“…Серотонин (5-НТ) -важный ней-ротрансмиттер, обусловливающий обоюдную комму-никацию между головным мозгом и кишечником [8]. Это вещество преимущественно вырабатывается энте-рохромаффинными клетками слизистой кишечника.…”