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Guanylyl cyclase-A receptor (GC-A), Guanylyl cyclase-B receptor (GC-B), Guanylyl cyclase-C receptor (GC-C) (GC-A (for type A), GC-B (for type B), GC-C (for type C))

Target
GC-A (for type A), GC-B (for type B), GC-C (for type C)
Molecular classification
Receptor (membrane-bound), Enzyme (guanylyl cyclase activity)
01

Overview

Particulate guanylyl cyclase receptors are a family of single-pass transmembrane enzymes whose extracellular domains bind specific peptide ligands (ANP/BNP for GC-A, CNP for GC-B, STa/guanylin/uroguanylin for GC-C), leading to intracellular catalytic conversion of GTP to cGMP. This second messenger drives diverse physiological effects including blood pressure regulation, natriuresis, antifibrotic actions, fluid secretion, and more. Mutations or dysregulation of these receptors are implicated in cardiovascular, renal, and gastrointestinal diseases. Therapeutic strategies include peptide mimetics and small molecule activators. Clarification is needed in literature to always specify the isoform (GC-A, GC-B, GC-C) since "particulate guanylate cyclase receptor" is too broad for clinical or molecular application.

Other names
GC-A (NPR-A)GC-B (NPR-B)GC-C (also known as STaR for heat-stable enterotoxin receptor)Natriuretic peptide receptor-A (NPR-A; for GC-A)Natriuretic peptide receptor-B (for GC-B)Natriuretic peptide receptor-C (note: NPR-C is not a cyclase but a clearance receptor; sometimes confused in literature)
02

Mechanism of action

Agonists/activators bind extracellular domain, stimulate receptor guanylyl cyclase activity, increase intracellular cGMP cGMP mediates vasodilation, natriuresis, antifibrotic effects, and more

03

Biological functions

Signal transduction via cGMP as a second messengerRegulation of blood pressure (GC-A)Natriuresis and diuresis (GC-A)Inhibition of renin-angiotensin-aldosterone system (GC-A)Cardiovascular remodeling suppression (GC-A)Anti-fibrotic effects (GC-B)Fluid/electrolyte regulation (GC-A, GC-B)Intestinal fluid secretion (GC-C)Phototransduction (RetGC isoform)
04

Disease associations

Cardiovascular disease (hypertension, heart failure; GC-A)Renal disease (GC-A, GC-B)Fibrosis (cardiorenal; GC-B)Gastrointestinal disease (GC-C)Potential roles in cancer and inflammation (GC-A, GC-C)
05

Safety considerations

Hypotension (as a result of excessive GC-A activation/vasodilation)Fluid/electrolyte abnormalities (natriuretic effects)Rapid peptide degradation can limit therapeutic efficacy (GC-B/CNP, addressed by drug design)Off-target effects in tissues expressing multiple subtypes
06

Interacting drugs

Peptide agonists: Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) for GC-A; C-type natriuretic peptide (CNP) for GC-B

4 more in the full profile.

07

Biomarkers

Plasma levels of ANP, BNP, CNP (for assessing GC-A/GC-B pathway activity)cGMP concentrations (tissue, plasma)

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