Localization of heme oxygenase-2 and modulation of cGMP levels by carbon monoxide and/or nitric oxide in the retina.
Heme oxygenase-2 (HO-2) synthesizes carbon monoxide (CO), a modulator of soluble guanylate cyclase (sGC). To examine this signal transduction pathway in the retina, we immunocytochemically localized HO-2, and investigated the effects of CO on cGMP levels. In turtle, HO-2-like immunoreactivity (-LI) was in all photoreceptors, some amacrine cells, and in numerous bipolar and ganglion cells. HO-2-LI colocalized with sGC activity in many cells. In rat, HO-LI was found only in the inner retina, in ganglion and amacrine cells. In turtle, stimulation with CO alone primarily increased cGMP-LI in bipolar cells in the visual streak. Stimulation with a combination of CO and nitric oxide (NO) dramatically increased cGMP-LI throughout the retina, in comparison to the smaller increases seen with NO or CO alone. These data suggest that CO is an endogenous modulator of the sGC/cGMP signaling pathway in many retinal neurons, and can dramatically amplify NO-stimulated increases in cGMP.
Department of Biology, Boston University, MA 02215, USA.
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D000818:Animals; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007395:Interneurons / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015398:Signal Transduction; D014426:Turtles
D004338:Drug Combinations; D007527:Isoenzymes; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D006152:Cyclic GMP