Atrial natriuretic peptide (
ANP) regulates a variety of physiological parameters, including the blood pressure and intravascular volume, by interacting with its receptors present on the plasma membrane.
ANP receptors are of three subtypes:
ANP-A, -B and -C receptors.
ANP-A and
ANP-B receptors are
guanylyl cyclase receptors, whereas
ANP-C receptors are coupled to
adenylyl cyclase inhibition or
phospholipase C activation through inhibitory
guanine nucleotide-regulating
protein. Unlike other
G protein-coupled receptors,
ANP-C receptors have a single transmembrane domain and a short cytoplasmic domain of 37
amino acids, the cytoplasmic domain has a structural specificity like those of other single-transmembrane-domain receptors and 37
amino-acid cytoplasmic domain peptide is able to exert is inhibitory effect on
adenylyl cyclase. The activation of
ANP-C receptor by C-ANP(4-23) (a ring-deleted
peptide of
ANP) and
C-type natriuretic peptide inhibits the
mitogen-activated protein kinase activity stimulated by
endothelin-3,
platelet-derived growth factor and phorbol-12
myristate 13-acetate. C-
ANP also inhibits
mitogen-induced stimulation of
DNA synthesis, indicating that the
ANP-C receptor plays a role in cell proliferation through an inhibition of
mitogen-activated protein kinase and suggesting that the
ANP-C receptor might also be coupled to other signal transduction mechanism(s) or that there might be an interaction of the
ANP-C receptor with some other signalling pathways.
ANP receptor binding is decreased in most organs in hypertensive subjects and hypertensive animals. This decrease is consistent with there being fewer
guanylyl cyclase-coupled receptors in the kidney and vasculature and selective inhibition of the
ANP-C receptor in the thymus and spleen. Platelet
ANP-C receptors are decreased in number in hypertensive patients and spontaneously hypertensive rats.
ANP-A, -B and -C receptors are decreased in number in
deoxycorticosterone acetate-
salt-treated kidneys and vasculature; however, the responsiveness of
adenylyl cyclase to
ANP is augmented in the vasculature and heart and is attenuated completely in platelets. These alterations in
ANP receptor subtypes may be related to the pathophysiology of
hypertension. Several
hormones such as
angiotensin II,
ANP and
catecholamines, the levels of which are increased in
hypertension, downregulate or upregulate
ANP-C receptors and
ANP-C receptor-mediated inhibition of
adenylyl cyclase. It can be suggested that the
antihypertensive action of several types of drugs such as
angiotensin converting enzyme inhibitors,
angiotensin type 1 receptor antagonists and
beta2-adrenergic antagonists may partly be attributed to their ability to modulate the expression and function of the
ANP-C receptor.