Pharmacology of serotonin: what a clinician should know

Abstract

SUMMARYThe pharmacology of serotonin (5-hydroxytryptamine or 5-HT) in the gut has been the centre of intense interest and research for several decades. Although it is now recognised that 5-HT is contained in intrinsic enteric neurones (where it works as a neurotransmitter), enterochromaffin cells of the mucosa are the main source (more than 90%) of the body's 5-HT. In the gut, 5-HT is an important mucosal signalling molecule targeting enterocytes, smooth muscle cells, and enteric neurones. Application of exogenous 5-HT evokes so many responses that it is difficult to determine which are physiologically relevant. This bewildering range of effects is largely due to the presence of multiple receptor subtypes, which appear to be present on several classes of myenteric neurones, on smooth muscle cells, and on epithelial cells. 5-HT is thought to be involved in the pathophysiology of several clinical entities such as functional gut disorders (namely, irritable bowel syndrome), carcinoid diarrhoea, and chemotherapy induced emesis. In this review, the possible targets for pharmacological intervention are analysed in the light of the most recent advances of our understanding of the role of 5-HT in gut pathophysiology. Indeed, the recent regulatory interventions on cisapride (a 5-HT 4 receptor partial agonist) and alosetron (a 5-HT 3 receptor antagonist) have prompted a rethinking of our approaches to the pharmacological modulation of serotonergic pathways. In gut disorders, the most interesting targets for pharmacological intervention are: (1) the 5-HT receptor subtypes known to affect gut function such as those belonging to the 5-HT 1 , 5-HT 3 , 5-HT 4 , and 5-HT 7 subtypes; and (2) the 5-HT reuptake mechanism which, apart from the central nervous system, is expressed in enteric neurones and enterocytes and is blocked by antidepressants.

Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome

“…Interestingly, the IBS-C patients in this population were the most responsive to vitamin D supplementation in terms of a striking improvement across nearly all IBS symptoms. 47 Because IBS-C patients are thought to possess lower gut serotonin levels, 48 the responsiveness of these patients to vitamin D supplementation is consistent with the actions of vitamin D to raise gut TPH1/serotonin levels 25 and with our current hypothesis that vitamin D, via induction of the intestinal TPH1 gene, may play a role in IBS pathophysiology. While this study was limited by its small sample size, our IBS cohort displayed a trend toward diminished serum vitamin D levels relative to our non-IBS control group.…”

Um marcador anatômico e a proposta de tratamento cirúrgico na síndrome do cólon irritável

“…Fatores culturais e decorrentes de hábitos alimentares têm sido isolados com sugestões de agentes etiológicos. 25,26 Hiperalgesia visceral, estresse, abuso físico e sexual têm sido elementos associados como participantes do conjunto de dados clínicos, englobado no universo dessa moléstia [1][2][3][4][5][6][7][8][9] , da mesma forma ocorrendo com as enterites bacterianas e virais, sem que, no entanto, seja possível destacar um elemento marcador. 27,28 São tantas as teorias e complexas as investigações e conclusões que a SCI passa a ser vista sob um conjunto heterogêneo de desordens com sintomas parecidos, mas de diferentes etiologias [29][30][31][32] que retroalimentam mais especulações sobre uma causa básica, o que, sem dúvida alguma, favorece a " medicalização" e a emergência de procedimentos subsidiados pela medicina alternativa 33 .…”

“…Apesar de ser comum, com incidência populacional de até 30% (predominando nas mulheres), e de ser alvo de estudos com destaque para diversos hormônios de ação gastrintestinal [3][4][5][6][7][8][9][10][11] , o diagnóstico e o tratamento dessa doença nem sempre são tarefas fáceis de serem executadas, sobretudo pela falta de um marcador que defina sua natureza, não só para retirá-la da classe de " doença de diagnóstico de exceção", como para permitir opções terapêuticas efetivas. 12,13 Baseados na observação de que a Síndrome do ceco móvel (SCM) engloba sintomas que se superpõem aos da SCI 14 nossos objetivos, ao desenvolver um estudo prospectivo não casualizado, foram: a. demonstrar a relação de causa e efeito entre o ceco móvel e a SCI, b. avaliar o resultado da cecopexia, como método de tratamento de pacientes com Síndrome do cólon irritável (SCI) ou com desconforto abdominal de etiologia desconhecida; e c. mostrar que o ceco móvel pode ser considerado como o primeiro marcador anatômico para a SCI.…”

Decreased Motility of the Lower Esophageal Sphincter in a Rat Model of Gastroesophageal Reflux Disease May Be Mediated by Reductions of Serotonin and Acetylcholine Signaling

“…It has been demonstrated that 5-HT 4 -receptor activation may be associated with esophageal peristalsis and LES tone. 9,12) Of the 5-HT receptor antagonists tested, contraction by 5-HT was significantly reduced by adding the 5-HT 4 receptor antagonist, but not by the 5-HT 3 receptor antagonist. Although, the 5-HT 2B receptor antagonist SB204741 and 5-HT 2C receptor antagonist SB242084 partly attenuated 5-HTinduced contraction in LES strips, LES contraction was not induced by the 5-HT 2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (data not shown in Figs.…”