J Physiol Volume 586, Number 2, 353-366, January 15, 2008 DOI: 10.1113/jphysiol.2007.144253
Natriuretic peptide C receptor signalling in the heart and vasculature
Robert A. Rose1 and
Wayne R. Giles2
1 Departments of Physiology and Medicine, Heart and Stroke/Richard Lewar Centre, University of Toronto and University Health Network, Toronto, Ontario, Canada
2
Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
Natriuretic peptides (NPs), including atrial, brain and C-type natriuretic peptides (ANP, BNP and CNP), bind two classes of cell surface receptors: the guanylyl cyclase-linked A and B receptors (NPR-A and NPR-B) and the C receptor (NPR-C). The biological effects of NPs have been mainly attributed to changes in intracellular cGMP following their binding to NPR-A and NPR-B. NPR-C does not include a guanylyl cyclase domain. It has been denoted as a clearance receptor and is thought to bind and internalize NPs for ultimate degradation. However, a substantial body of biochemical work has demonstrated the ability of NPR-C to couple to inhibitory G proteins (Gi) and cause inhibition of adenylyl cyclase and activation of phospholipase-C. Recently, novel physiological effects of NPs, mediated specifically by NPR-C, have been discovered in the heart and vasculature. We have described the ability of CNP, acting via NPR-C, to selectively inhibit L-type calcium currents in atrial and ventricular myocytes, as well as in pacemaker cells (sinoatrial node myocytes). In contrast, our studies of the electrophysiological effects of CNP on cardiac fibroblasts demonstrated an NPR-C–Gi–phospholipase-C-dependent activation of a non-selective cation current mediated by transient receptor potential (TRP) channels. It is also known that CNP and BNP have important anti-proliferative effects in cardiac fibroblasts that appear to involve NPR-C. In the mammalian resistance vessels, including mesenteric and coronary arteries, CNP has been found to function as an NPR-C-dependent endothelium-derived hyperpolarizing factor that regulates local blood flow and systemic blood pressure by hyperpolarizing smooth muscle cells. In this review we highlight the role of NPR-C in mediating these NP effects in myocytes and fibroblasts from the heart as well as in vascular smooth muscle cells.
(Received 31 August 2007;
accepted after revision 12 November 2007;
first published online 15 November 2007)
Corresponding authors R. A. Rose: Heart and Stroke/Richard Lewar Centre, Fitzgerald Building, Rm 67, 150 College Street, Toronto, Ontario, Canada M5S 3E2. Email: rob.rose{at}utoronto.ca; W. R. Giles: Office of the Dean, Faculty of Kinesiology, University of Calgary, 2500 University Drive N.W., Calgary, Alberta, Canada T2N 1N4. Email: wgiles{at}ucalgary.ca
Copyright © 2008 The Physiological Society.
