Natriuretic peptide receptor 1 (NPR1) (NPR1)

Particulate guanylyl cyclase (pGC) receptors in the kidney, primarily Natriuretic Peptide Receptor 1 (NPR1, also known as GC-A) and Natriuretic Peptide Receptor 2 (NPR2, also known as GC-B), are membrane-bound enzymes that serve as critical regulators of cardiorenal homeostasis. These receptors are activated by natriuretic peptides, including Atrial Natriuretic Peptide (ANP), B-type Natriuretic Peptide (BNP), and C-type Natriuretic Peptide (CNP), which are released in response to cardiac stretch or endothelial signals. Upon activation, the intracellular catalytic domain of the receptor converts GTP into the second messenger cyclic GMP (cGMP), which subsequently activates protein kinase G (PKG) to mediate various physiological effects. In the kidney, this signaling pathway promotes natriuresis, diuresis, and an increase in the glomerular filtration rate (GFR) by dilating afferent arterioles and inhibiting sodium reabsorption in the collecting ducts. Furthermore, these receptors exert anti-fibrotic, anti-inflammatory, and anti-apoptotic effects, making them attractive therapeutic targets for heart failure, hypertension, and chronic kidney disease. Pharmacological strategies include the use of recombinant natriuretic peptides like nesiritide and novel designer agonists like cenderitide, although systemic hypotension remains a significant dose-limiting challenge.

Other names

Natriuretic peptide receptor ANPR-AGuanylate cyclase AGC-AGUCY2AParticulate guanylyl cyclase AAtrial natriuretic peptide receptor ANatriuretic peptide receptor 1

Agonism (activation of the intracellular guanylyl cyclase domain to increase cGMP production)