Localization of natriuretic peptides and their activation of particulate guanylate cyclase and nitric oxide synthase in the retina

In the vertebrate retina, cyclic guanosine monophosphate (cGMP) mediates ph otoreceptor signal transduction and modulates ion channel and gap junction conductivity. Although most previous studies have focused on its synthesis by nitric oxide (NO)-sensitive soluble guanylate cyclase, cGMP is also synt hesized by NO-insensitive particulate guanylate cyclases (pGC). Natriuretic peptides and their associated pGC-coupled receptors have been reported in retina, but few studies have localized these natriuretic peptides or pGCs t o specific retinal cells or demonstrated that activation of pGCs by natriur etic peptides increases cGMP synthesis. In this study, we immunocytochemica lly localized atrial, brain, and C-type natriuretic peptide-like immunoreac tivity (ANP-LI, BNP-LI, and CNP-LI, respectively) in turtle retina by using isoform specific antisera, and determined the ability of each natriuretic peptide isoform to increase cGMP-like immunoreactivity (cGMP-LI) in retinal cells. ANP-LI and CNP-LI were localized in sparsely distributed amacrine c ells with thin, intermittently varicose processes in the inner plexiform la yer. BNP-LI was localized to abundant somata in the inner nuclear and gangl ion cell layers and in specific amacrine and horizontal cells. Stimulation of turtle eyecups with each of these natriuretic peptides increased cGMP-LI in multistratified amacrine cells by means of NO-independent mechanisms in the central retina, and in select amacrine and bipolar cells in the periph eral retina by a nitric oxide-dependent mechanism. These results indicate t hat natriuretic peptides can modulate the synthesis of cGMP in select retin al neurons by two distinct signal transduction pathways in a regionally spe cific manner. (C) 2000 Wiley-Liss, Inc.