Section of Gastroenterology, Boston University School of Medicine, Boston, Massachusetts, USA.
Curr Opin Endocrinol Diabetes Obes. 2018 Feb;25(1):12-21. doi: 10.1097/MED.0000000000000383.
To summarize the most recent findings relevant to the biology of serotonin (5-hydroxytryptamine; 5-HT) and the enzyme tryptophan hydroxylase (TPH) in human gastrointestinal disease.
Serotonin is synthesized in the central nervous system (CNS) and the gastrointestinal tract where it is secreted from enteroendocrine cells. Its biosynthesis is regulated by two isoforms of the enzyme TPH of which TPH1 is localized predominantly in gastrointestinal enteroendocrine cells. Serotonin activates the peristaltic reflexes, regulates gastrointestinal motility, and has a role in intestinal inflammation. Inhibition of TPH with novel molecules represents a new pharmacological tool in the successful management of carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors (GI-NETs). Certain 5-HT receptor subtype agonists and antagonists are useful in the treatment of functional gastrointestinal disorders.
The gastrointestinal tract is the largest storage organ for serotonin where its biosynthesis is regulated by TPH1. It has several important functions in gastrointestinal motility, secretion, and inflammation. Furthermore, TPH represents a target for inhibitory pharmacological therapy of serotonin access states such as the carcinoid syndrome.
总结与人类胃肠道疾病中血清素(5-羟色胺;5-HT)和色氨酸羟化酶(TPH)的生物学相关的最新发现。
血清素在中枢神经系统(CNS)和胃肠道中合成,在那里它从肠内分泌细胞中分泌出来。其生物合成受两种 TPH 同工酶调节,其中 TPH1 主要定位于胃肠道肠内分泌细胞中。血清素激活蠕动反射,调节胃肠道蠕动,在肠道炎症中起作用。用新型分子抑制 TPH 是成功治疗胃肠道神经内分泌肿瘤(GI-NETs)患者类癌综合征的新药理学工具。某些 5-HT 受体亚型激动剂和拮抗剂可用于功能性胃肠道疾病的治疗。
胃肠道是血清素的最大储存器官,其生物合成受 TPH1 调节。它在胃肠道动力、分泌和炎症中具有多种重要功能。此外,TPH 是抑制血清素摄取状态(如类癌综合征)的药理学治疗的靶点。