Soluble guanylate cyclase 1 (sGC1)

Soluble guanylate cyclase 1 (GC-1) is a heterodimeric enzyme, typically composed of alpha-1 and beta-1 subunits, that functions as the primary intracellular receptor for nitric oxide (NO) (NIH.gov, ACS.org). Upon activation by NO binding to its prosthetic heme group, GC-1 catalyzes the conversion of guanosine triphosphate (GTP) into the second messenger cyclic guanosine monophosphate (cGMP) (NIH.gov). This signaling cascade plays a vital role in cardiovascular homeostasis by mediating vasodilation, inhibiting platelet aggregation, and preventing pathological vascular remodeling (NIH.gov, ERSnet.org). Dysregulation of the NO-sGC-cGMP pathway is implicated in several diseases, most notably pulmonary arterial hypertension (PAH) and heart failure, where reduced NO bioavailability or sGC oxidation impairs signaling (NIH.gov, MDPI.com). Therapeutic strategies targeting GC-1 include sGC stimulators, which enhance the enzyme's response to NO, and sGC activators, which can stimulate the enzyme even in its oxidized or heme-deficient states (NIH.gov). Drugs such as riociguat and vericiguat have been successfully developed to treat these conditions, though they require careful monitoring for side effects like hypotension (ERSnet.org, MDPI.com).

Other names

GC-1sGC1sGC alpha-1/beta-1Soluble guanylyl cyclase 1Nitric oxide receptorGuanylate cyclase 1GUCY1A1/GUCY1B1 complex

Soluble guanylate cyclase (sGC) stimulators (e.g., riociguat, vericiguat) act by sensitizing the enzyme to endogenous nitric oxide (NO) and directly stimulating the reduced, heme-containing form of sGC. sGC activators (e.g., cinaciguat) target the oxidized or heme-free form of the enzyme, which is unresponsive to NO, to restore cGMP production under conditions of oxidative stress (NIH.gov).