Schematic structures of natriuretic peptides and their receptors. A: proANP1–126 with its signal peptide is cleaved to NT-proANP1–98 and the active hormone ANP1–28 by corin, a trypsin-like serine protease on cell surface (open arrow). Binding ANP to the extracellular ligand-binding (ELB) domain of natriuretic peptide receptor A (NPR-A) induces the particulate guanylyl cyclase (GC) catalytic domain to generate cGMP from guanosine triphosphate (GTP) as second messenger to inhibit cyclic nucleotide-gated ion channels and Na+-K+-adenosine triphosphatase (Na+-K+-ATPase), as well as activate protein kinase G and phosphodiesterase for target cells to exert effects. B: proBNP1–108 with its signal peptide is cleaved to NT-proBNP1–76 and the active hormone BNP1–32 by furin, an intracellular pro-protein convertase, and corin (open arrow). C: proCNP1–103 with its signal peptide is cleaved to NT-proCNP1–81 (50) and the active hormones CNP1–22 and CNP1–53 by proteolytic enzymes such as furin (open arrows). x, Site of neprilysin (NEP) action (29, 57, 58). D: binding ANP, BNP, or CNP to natriuretic peptide receptor C (NPR-C) induces internalization (endocytosis), resulting in lysosomal degradation of ANP, BNP, and CNP, and reappearance of the NPR-C in the cell membrane (43, 58). NPR-B, natriuretic peptide receptor B; PKL, protein kinase-like homology domain; TS, transmembrane spanning region.
Cover: From material detailed in the following article: Bell FE, Wilson LB, Hoppmann RA. Using ultrasound to teach medical students cardiac physiology. Adv Physiol Educ 39: 392–396, 2015; doi:10.1152/advan.00123.2015.