REVIEW: Membrane Guanylyl Cyclases as Potential Targets for Guanylin Action

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Elizaveta D. Snigireva^1,a* and Olga V. Smirnova¹

¹Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: May 20, 2025; Revised: August 27, 2025; Accepted: September 14, 2025

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Guanylins are intestinal natriuretic peptides that regulate water and electrolyte balance in the intestine and kidney. Their primary receptor is membrane guanylyl cyclase C (GC-C), while alternative functions related to feeding behavior and olfactory preferences are mediated by guanylyl cyclase D (GC-D) expressed exclusively in olfactory neurons. Evidence suggests existence of unidentified receptors activated by guanylin peptides in the absence of GC-C that affect sodium metabolism. Some of these receptors trigger the cGMP-dependent signaling pathways typical exclusively for guanylyl cyclases. This review provides a comparative analysis of the existing data on different membrane receptor guanylyl cyclases, including early discoveries and contemporary research, focusing on their potential as guanylin targets.

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KEY WORDS: membrane guanylyl cyclases, GC-A, GC-B, GC-C, GC-D, GC-E, GC-F, GC-G, guanylin, uroguanylin

DOI: 10.1134/S000629792560156X

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