Atrial natriuretic factor

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natriuretic peptide precursor A
Symbol(s):	NPPA ANP, PND
Locus:	1 p36.21
EC number	[1]
EntrezGene	4878
OMIM	108780
RefSeq	NM_006172
UniProt	P01160

Atrial natriuretic factor (ANF), atrial natriuretic peptide (ANP) or atriopeptin, is a polypeptide hormone involved in the homeostatic control of body water,sodium, and adiposity. It is released by atrial myocytes, cells in the atria of the heart, in response to signals of raised blood pressure and acts to reduce the water, sodium and adipose loads on the circulatory system, thereby returning blood pressure to more normal levels.

Structure

ANP is a 28 amino acid peptide with a 17 AA ring, and is closely related to BNP (Brain Natriuretic Peptide, but produced largely in the heart) and CNP (C-type Natriuretic Peptide) which all share the same amino acid ring. ANP was discovered in 1981 by a team in Ottawa led by Mercedes Kuroski de Bold after they made the seminal observation that injection of atrial (but not ventricular) tissue extracts into rats caused copious natriuresis.

Production

ANP is produced, stored and released by cells present in the atria of the heart, atrial myocytes. It is released in response to a variety of signals, the signals, present when the subject is hypervolaemic, exercised or calorically restricted.

It is secreted in response to:

• Atrial distention, stretching
• Sympathetic stimulation of β-adrenoceptors
• Raised sodium concentration
• Angiotensin-II
• Endothelin, a potent vasoconstrictor

Causes of stretching include high extracellular fluid volume, high blood volume, and atrial fibrillation. Notably, it is secreted in response to immersion of the body in water, which causes an atrial stretch due to altered distribution of intravascular fluid. It has been shown that in horses, it is also released in response to exercise.

Receptors

There are three distinct receptors identified so far in mammals, natriuretic peptide receptors A, B and C (NPRA or NPR1, NPRB or NPR2 and NPRAC or NPR3).

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

Physiological effects

The overall effects of ANP release are a reduction in blood volume and therefore central venous pressure, cardiac output, and arterial blood pressure. It increases renal sodium secretion and excretion. It also increases lipolysis.

The overall effect of which is to counter the blood pressure-raising effects of the renin-angiotensin system.

Renal

• Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the mesangial cells. This increases the glomerular filtration rate, resulting in greater excretion of sodium and water.

• Decreases sodium resorption in the renal distal convoluted tubule and cortical collecting duct.

• Inhibits renin secretion.

Vascular

• Relaxes vascular smooth muscle in arterioles and venules by:
  • Receptor-mediated elevation of vascular smooth muscle cGMP
  • Inhibition of the effects of catecholamines

Adrenal

• Reduces aldosterone secretion by the adrenal cortex.

Adipose Tissue

• Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
• Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
• Increases intracellular guanosine 3',5'-cyclic monophosphate cyclic GMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP dependent protein kinase-I cGK-I
• Does not modulate cAMP production or PKA activity

Degradation

Degradation of ANP is needed for its actions to be stopped. It is broken down by an enzyme, neutral endopeptidase (NEP). Recently inhibitors of NEP have been developed, although have not yet been licenced, proving to be beneficial in congestive heart disease.

Other natriuretic factors

In addition to the mammalian natriuretic factors (ANP, BNP, CNP), two other peptides have been isolated. Tervonen (1998) described a salmon natriuretic factor (Salmon cardiac peptide) with a similar structure and properties and Dendroaspis Natriuretic Peptide (DNP) was discovered in the venom of the green mamba by Schweitz et al. (1992).

References

Sengenes C, Moro C, Galitzky J, Berlan M, Lafontan M. 2005 Natriuretic peptides: a new lipolytic pathway in human fat cells Med Sci (Paris) Dec;21 Spec No:29-33

De Bold AJ 1985 Atrial natriuretic factor: a hormone produced by the heart. Science 230:767–770.

Joshi Venugopal, Pharmacological Modulation of the Natriuretic Peptide System, Expert Opinion in Therapuetic Patents, 2003, Vol. 13, No. 9, Pages 1389-1409.[2]

Clemo HF, Baumgarten CM, Stambler BS, Wood MA, Ellenbogen KA. Atrial natriuretic factor: implications for cardiac pacing and electrophysiology. PACE Pacing Clin Electrophysiol. 1994;17:70-91.

Tervonen et al., 1998 Endocrinology 139:4021-4025.

Kokkonen et al., 2000 Am J Physiol 278: E285-E292.

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Target-derived NGF, BDNF, NT-3

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Urinary system - Kidney
Renal capsule | Renal cortex | Renal medulla (Renal sinus, Renal pyramids) | Renal calyx | Renal pelvis
Nephron - Renal corpuscle (Glomerulus, Bowman's capsule) → Proximal tubule → Loop of Henle → Distal convoluted tubule → Collecting ducts Juxtaglomerular apparatus (Macula densa, Juxtaglomerular cells) Renal circulation - Renal artery → Interlobar arteries → Arcuate arteries → Cortical radial arteries → Afferent arterioles → Glomerulus → Efferent arterioles → Vasa recta → Arcuate vein → Renal vein
Renal physiology
Filtration - Ultrafiltration | Countercurrent exchange Hormones effecting filtration - Antidiuretic hormone (ADH) | Aldosterone | Atrial natriuretic peptide Endocrine - Renin | Erythropoietin (EPO) | Calcitriol (Active vitamin D) | Prostaglandins
Assessing Renal function / Measures of Dialysis
Glomerular filtration rate | Creatinine clearance | Renal clearance ratio | Urea reduction ratio | Kt/V | Standardized Kt/V | Hemodialysis product

de:Atriales natriuretisches Peptid ja:心房性ナトリウム利尿ペプチド mk:Aтријален натриумуретичен пептид pl:Przedsionkowy peptyd natriuretyczny