Cyclic GMP signaling in podocytes

Abstract

Natriuretic peptides (NP), together with nitric oxide (NO) are powerful relaxing factors acting via a common second messenger, cyclic GMP (cGMP). Together with other vasoactive modulators, these vasorelaxing factors play an essential role in regulating the function of kidney glomeruli. The presence of NP receptors in podocytes has been well documented. Recently, also mRNA for soluble guanylate cyclase, the NO receptor, has been shown in these cells. Stimulation of podocytes with atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and NO donors results in considerable upregulation of cellular cGMP synthesis. The podocyte foot processes contain a highly organized network of microfilaments adhering to the glomerular basement membrane (GBM). Changes in podocyte cytoskeleton accompanied by detachment of the cells from the GBM are closely associated with many glomerulopathies. The contractile apparatus in the podocyte foot processes seems to be an obvious target for the cyclic GMP signaling cascade. However, little is known about implications of the cGMP synthesis in these cells. We briefly review the current art regarding generation and modulation of cyclic GMP levels in podocytes. We discuss also the possible targets for this secondary messenger as well as its functional role in podocytes.