Atrial natriuretic peptide receptor

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An atrial natriuretic peptide receptor is a receptor for atrial natriuretic peptide. [1]

Contents

Mechanism

NPRA and NPRB are linked to guanylyl cyclases, while NPRC is G-protein-linked and is a "clearance receptor" that acts to internalise and destroy the ligand.

ANP activation of the ANP catalytic receptor will stimulate its intracellular guanylyl cyclase activity to convert GTP to cGMP. cGMP will then stimulate cGMP-dependent protein kinase (PKG), which will then induce smooth muscle relaxation. This is particularly important in the vasculature, where vascular smooth muscle will bind ANP released as a result of increasing right atrial pressure and will cause the walls of the vasculature to relax. This relaxation will decrease total peripheral resistance, which will in turn decrease venous return to the heart. The decrease in venous return to the heart will reduce the preload and will result in the heart's having to do less work.

There is also a soluble guanylyl cyclase that cannot be stimulated by ANP. Instead, vascular endothelial cells will use L-arginine to make nitric oxide via nitric oxide synthase. The nitric oxide will then diffuse into the vascular smooth muscle and will activate the soluble guanylyl cyclase. The subsequent increase in cGMP will cause vasodilation with the same effects as described above. This is why nitroglycerine is given to a person having a heart attack. The nitroglycerine will be metabolized to nitric oxide, which will stimulate soluble guanylyl cyclase. This will result in a decrease in total peripheral resistance and a decrease in preload on the heart. As a result, work done by the heart will decrease and will allow the heart to contract less strongly. Weaker contractions will lead to more blood flow in the coronary arteries, which will help the ischemic cardiac myocytes.

Types

There are three distinct atrial natriuretic factor receptors identified so far in mammals: natriuretic peptide receptors 1, 2, and 3.

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Atrial natriuretic peptide

Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides are a family of hormone/paracrine factors that are structurally related. The main function of ANP is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion. ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. These cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume.

Vasodilation

Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, which is the narrowing of blood vessels.

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Soluble guanylyl cyclase

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NPR1

Natriuretic peptide receptor A/guanylate cyclase A , also known as NPR1, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR1 gene.

NPR3

Natriuretic peptide receptor C/guanylate cyclase C , also known as NPR3, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR3 gene.

GUCY1B3

Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene.

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Ventricular natriuretic peptide

Ventricular natriuretic peptide or brain natriuretic peptide (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume.

Scott A. Waldman is a medical doctor and biomedical scientist at Sidney Kimmel Medical College of Thomas Jefferson University, where he is the Samuel M.V. Hamilton Professor of Medicine, and also tenured Professor and chair of the Department of Pharmacology & Experimental Therapeutics. He is author of a pharmacology textbook, and former chief editor of Clinical Pharmacology & Therapeutics. He is known for his work in atrial natriuretic factor intracellular signaling through guanylate cyclase (GC), the relation of Guanylyl cyclase C (GC-C) to the pathogenesis of colorectal cancer Also for his hypotheses concerning the roles of intestinal paracrine hormones in satiety, obesity and cancer risk. Waldman also holds concurrent positions as Adjunct Professor at the University of Delaware, School of Health Sciences.

References

  1. Hirose S, Hagiwara H, Takei Y (August 2001). "Comparative molecular biology of natriuretic peptide receptors". Can. J. Physiol. Pharmacol. 79 (8): 665–72. doi:10.1139/cjpp-79-8-665. PMID   11558675.