钠尿肽C型受体信号通路与心血管疾病

Signaling pathway of natriuretic peptide C receptor in cardiovascular diseases

钠尿肽家族（natriuretic peptides,NPs）主要包括心房钠尿肽（atrial natriuretic peptide,ANP）、脑钠尿肽（brain natriuretic peptide,BNP）和C型钠尿肽（Ctypenatriuretic peptide,CNP）3类,新发现的还有曼巴蛇钠尿肽、尿扩张素及在澳大利亚大班蛇毒液中的一类钠尿肽样肽类[1]。钠尿肽激素在心血管、肾脏、内分泌系统中的作用研究比较清楚,

Natriuretic peptide C receptor（NPR-C） has been described,at the time of its discovery,as a clearance receptor of natriuretic peptides（NPs） devoid of any physiological functions and does not contain a guanylyl cyclase domain.However,accumulated evidence indicates recently that NPR-C is coupled to an inhibitory heterotrimeric G protein,thus inhibiting the activity of adenylyl cyclase,decreasing intracellular cAMP levels and activating phospholipase C.NPs have an important role in the heart and vasculature that are specifically mediated by NPR-C signaling.In myocardial cells and pacing cells,C-type natriuretic peptide（CNP） inhibits L-type Ca2＋ current（Ica,L） via NPR-C.In myocardial fibroblasts,NPR-C-Gi-phospholipase C-dependent activation of a non-selective cation current can mediate antifibrotic and antiproliferative effects of CNP and brain natriuretic peptide（BNP）.In the mammalian resistance vessels,CNP functions 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,the regulatory role of signal transduction mediated by NPR-C in cardiovascular diseases is described.