Functional Properties and Dynamics of Natriuretic Peptide Receptors

Abstract

ince the discovery of atrial natriuretic factor (ANF or ANP) in 1981 by De Bold et al. (l), S more than 6500 articles on the subject have appeared in the literature. For an extensive review on ANP and its receptors, the reader is directed to Reference 2. In this short review, we will consider in a noninclusive manner the dynamics and functional properties of natriuretic peptide receptors. ANP is a 28-amino acid polypeptide hormone secreted mainly by the heart atria in response to atrial stretch that results from an increase in central venous pressure, or systemic and pulmonary hypertension. ANP is a member of a family of natriuretic peptides, which include B-type or brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and urodilatin. The physiological role of BNP, CNP, and urodilatin remains essentially unknown.The main actions of ANP in the mammalian organism are geared toward the regulation of volumepressure homeostasis (2,3). In the kidney, ANP exerts hemodynamic and tubular actions that lead to diuresis and natriuresis. In the cardiovascular system, ANP acts as a strong antagonist of vasoconstriction and also decreases plasma volume, a combination of events that reduces blood pressure. The decrease in plasma volume is due to a shift of fluid from the intravascular to the interstitial compartment brought about by an increase in hydraulic permeability of systemic capillaries. ANP is also a powerful functional antagonist of the renin-angiotensin-aldosterone system through inhibiting renin secretion by the kidney, aldosterone synthesis by the adrenal, and by antagonizing all known peripheral actions of angiotensin 11. The inhibition of the activity and effects of renin-angiotensinaldosterone contributes substantially to the cardiovas-' To whom requests for reprints should be addressed

A novel promoter variant of the natriuretic peptide clearance receptor gene is associated with lower atrial natriuretic peptide and higher blood pressure in obese hypertensives

“…The clearance receptor for natriuretic peptides (NPRC), a candidate gene for essential hypertension, plays a key role in the regulation of plasma levels and biological effects of natriuretic peptides [1].…”

Natriuretic peptides and cardiovascular damage in the metabolic syndrome: molecular mechanisms and clinical implications

“…NPR-C is widely expressed in a variety of tissues, including adipose tissue. Although it has been reported that this receptor induces a G-protein-linked cAMP activation [13] and, thus is involved in the cellular mechanisms of the antigrowth properties of NPs, it is generally accepted that NPR-C plays a major role in the local modulation of the physiological effects of NPs, by modulating the final ANP and BNP binding to NPR-A and by acting as the clearance receptor of NPs [14]. Both ANP and BNP are rapidly removed from the circulation by this receptor [15].…”

Absence of somatic mutations in natriuretic peptide receptor type A gene in human aldosterone-secreting adenomas

“…Cardiac natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are potent inhibitors of aldosterone secretion (Anderson et al 1986, Holmes et al 1993, being effective antagonists of angiotensin II. The effects of both ANP and BNP on aldosterone secretion are mediated by natriuretic peptide receptor type A (NPRA, codified by the Npr1 gene), a membrane guanylyl cyclase with cGMP being the main intracellular messenger (Maack et al 1996).…”