The functional genomics of guanylyl cyclase/natriuretic peptide receptor-A: Perspectives and paradigms

Abstract

The cardiac hormones atrial natriuretic peptide and B-type natriuretic peptide (brain natriuretic peptide) activate guanylyl cyclase (GC)-A/natriuretic peptide receptor-A (NPRA) and produce the second messenger cGMP. GC-A/NPRA is a member of the growing family of GC receptors. The recent biochemical, molecular and genomic studies on GC-A/NPRA have provided important insights into the regulation and functional activity of this receptor protein, with a particular emphasis on cardiac and renal protective roles in hypertension and cardiovascular disease states. The progress in this field of research has significantly strengthened and advanced our knowledge about the critical roles of Npr1 (coding for GC-A/NPRA) in the control of fluid volume, blood pressure, cardiac remodeling, and other physiological functions and pathological states. Overall, this review attempts to provide insights and to delineate the current concepts in the field of functional genomics and signaling of GC-A/NPRA in hypertension and cardiovascular disease states at the molecular level. Molecular approaches to delineate the functional roles of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) in physiological and pathophysiological disease states including high blood pressure, cardiac hypertrophy, and congestive heart failure are described here. Comparative analyses of biochemical properties and physiological genomics of Npr1 gene should provide enormous potentials in understanding the biological functions of GC-A/NPRA signaling in hypertension and cardiovascular regulation at the molecular level. © 2011 FEBS.