Vascular Action Natriuretic Peptide Receptors

Discovery of structurally related natriuretic peptide hormones: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) suggests that their role in control of body fluid and blood pressure homeostasis is complex. This complexity is further enhanced by the existence of at least three types of natriuretic peptide receptors, designated as Npra (GC-A), Nprb (GC-B), and Nprc (clearance receptor) (1-3). Although these three natriuretic peptides have highly homologous structure, they also have distinct sites of synthesis, bind to specific receptors, and probably elicit discrete biological functions (1-3). Both Npra and Nprb belong to the members of receptor guanylyl cyclase (GC) family, which produce their own second messenger cyclic guanosine monophosphate (cGMP). Production of cGMP in response to natriuretic peptides results from their binding to the extracellular domain of Npra or Nprb, which probably allosterically regulates an increased activity of the intracellular GC catalytic domain (3, 4). The extracellular domain of Npra and Nprb is homologous to Nprc which apparently does not contain a GC catalytic domain. ANP and BNP bind to Npra and CNP binds to Nprb; however, all three natriuretic peptides indiscriminately bind to Nprc (4). CNP is a natural ligand for Nprb and is the prominent cGMP-generating and the biologically active receptor in vascular smooth muscle cells (VSMC). These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.