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 photoreceptor 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 synthesized 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 to specific retinal cells or demonstrated that activation of pGCs by natriuretic peptides increases cGMP synthesis. In this study, we immunocytochemically localized atrial, brain, and C-type natriuretic peptide-like immunoreactivity (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 cells with thin, intermittently varicose processes in the inner plexiform layer. BNP-LI was localized to abundant somata in the inner nuclear and ganglion 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 peripheral retina by a nitric oxide-dependent mechanism. These results indicate that natriuretic peptides can modulate the synthesis of cGMP in select retinal neurons by two distinct signal transduction pathways in a regionally specific manner.
Department of Biology, Boston University, Boston, Massachusetts 02215, USA.
T A
TA
Blute
H K
HK
Lee
T
T
Huffmaster
S
S
Haverkamp
W D
WD
Eldred
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism* / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D014426:Turtles / Q000033:anatomy & histology / Q000378:metabolism*
D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP