期刊
GUT
卷 67, 期 8, 页码 1543-1552出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2018-316029
关键词
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资金
- National Institutes of Health [R01 CA206026, R01 CA204881, P30 CA56036, R01DK92179]
- Synergy Pharmaceuticals, Inc.
- Targeted Diagnostic and Therapeutics, Inc.
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.
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