Guanylate cyclase A (GC-A) (GC-A)

Guanylate cyclase A (GC-A), also known as natriuretic peptide receptor A, is a single membrane-spanning enzyme that serves as the primary receptor for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It catalyzes the conversion of GTP to cyclic GMP (cGMP), which activates downstream protein kinase G to promote vasodilation, regulate blood pressure, and inhibit cellular growth and proliferation. GC-A is predominantly expressed in tissues such as the kidney, brain, and vascular endothelium, where it plays key roles in maintaining cardiovascular homeostasis, angiogenesis, liver regeneration, and lipolysis in adipose tissue. Dysregulation of the GC-A pathway contributes to cardiovascular diseases, including hypertension and heart failure, by impairing natriuretic peptide signaling and leading to fluid overload and vascular remodeling. Unlike soluble guanylate cyclase, which responds to nitric oxide, GC-A is activated extracellularly by peptide ligands binding to its extracellular domain, inducing conformational changes that enhance its intracellular catalytic activity. Although no drugs directly target GC-A clinically, its modulation holds therapeutic potential for cardiovascular disorders, distinct from approved sGC stimulators like riociguat used in pulmonary hypertension.

Other names

natriuretic peptide receptor Aatrial natriuretic peptide receptor Aparticulate guanylyl cyclase A

Activation by natriuretic peptides (e.g., ANP, BNP) leading to GTP conversion to cGMP, which activates protein kinase G for vasodilation and growth regulation; no direct small-molecule agonists approved for GC-A