Miner Philip B
a Oklahoma Foundation for Digestive Research, retired , Oklahoma City , OK , USA.
Expert Opin Pharmacother. 2018 Feb;19(2):177-183. doi: 10.1080/14656566.2018.1427733. Epub 2018 Jan 29.
Uroguanylin interacting with intestinal Guanylate Cyclase C (GC-C) receptors plays an important role in gastrointestinal fluid and electrolyte homeostasis. Plecanatide is the first uroguanylin analog that stimulates GC-C receptors on gastrointestinal mucosa with pH-sensitive receptor binding. Binding to the GC-C receptor activates intracellular conversion of GTP to cGMP resulting in the stimulation of intestinal fluid secretion. Areas covered: Herein, all published research regarding the development of and clinical experience with plecanatide is reviewed. Clinical study results in patients with Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with Constipation (IBS-C) are also reviewed. Success in the treatment of CIC and IBS-C is supported by beneficial effects on stool viscosity, Complete Spontaneous Bowel Movements and visceral sensation. Finally, the discussion within focuses on the importance of plecanatide in understanding the physiology of uroguanylin, the pathophysiology of IBS-C and the potential for development of uroguanylin and guanylin analogs. Expert opinion: Given this broad spectrum of potential activity for GC-C agonists, it would not be surprising to see that the use of agents such as plecanatide in new areas grow to a level even greater than the use for the present CIC and IBS-C indications.
尿鸟苷素与肠道鸟苷酸环化酶C（GC-C）受体相互作用，在胃肠道液体和电解质稳态中发挥重要作用。普卡那肽是首个尿鸟苷素类似物，它通过pH敏感的受体结合刺激胃肠道黏膜上的GC-C受体。与GC-C受体结合会激活细胞内GTP向cGMP的转化，从而刺激肠道液体分泌。涵盖领域：本文综述了所有已发表的关于普卡那肽的研发及临床经验的研究。还综述了慢性特发性便秘（CIC）和便秘型肠易激综合征（IBS-C）患者的临床研究结果。对粪便黏稠度、完全自主排便和内脏感觉的有益作用支持了CIC和IBS-C治疗的成功。最后，讨论聚焦于普卡那肽在理解尿鸟苷素生理学、IBS-C病理生理学以及尿鸟苷素和鸟苷素类似物开发潜力方面的重要性。专家观点：鉴于GC-C激动剂具有如此广泛的潜在活性，看到普卡那肽等药物在新领域的使用增长到甚至超过目前用于CIC和IBS-C适应症的水平也就不足为奇了。
