Functional gastrointestinal disorders (FGIDs) and IBDs are two of the most prevalent disorders of the GI tract and consume a significant proportion of healthcare resources. Recent studies have shown that membrane-bound guanylate cyclase-C (GC-C) receptors lining the GI tract may serve as novel therapeutic targets in the treatment of FGIDs and IBDs. GC-C receptor activation by its endogenous paracrine hormones uroguanylin and guanylin, and the resulting intracellular production of its downstream effector cyclic GMP, occurs in a pH-dependent manner and modulates key physiological functions. These include fluid and electrolyte homeostasis, maintenance of the intestinal barrier, anti-inflammatory activity and regulation of epithelial regeneration. Studies of the GC-C paracrine signalling axis have revealed the therapeutic potential of these receptors in treating GI disorders, including chronic idiopathic constipation and irritable bowel syndrome–constipation. This review focuses on the evolving understanding of GC-C function in health and disease, and strategies for translating these principles into new treatments for FGIDs and IBDs.

中文翻译：

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鸟苷酸环化酶-C 作为胃肠道疾病的治疗靶点

功能性胃肠道疾病 (FGID) 和 IBD 是两种最常见的胃肠道疾病，消耗很大一部分医疗资源。最近的研究表明，胃肠道内膜结合鸟苷酸环化酶-C (GC-C) 受体可能作为 FGID 和 IBD 治疗的新治疗靶点。GC-C 受体通过其内源性旁分泌激素尿鸟苷蛋白和鸟苷蛋白激活，并由此产生其下游效应器环 GMP，以 pH 依赖性方式发生并调节关键的生理功能。这些包括液体和电解质稳态、肠道屏障的维持、抗炎活性和上皮再生的调节。对 GC-C 旁分泌信号轴的研究揭示了这些受体在治疗胃肠道疾病（包括慢性特发性便秘和肠易激综合征 - 便秘）方面的治疗潜力。本综述重点关注对 GC-C 在健康和疾病中的功能不断发展的理解，以及将这些原理转化为 FGID 和 IBD 新疗法的策略。