Nitric oxide modulates cGMP levels in neurons of the inner and outer retina in opposite ways.
In the mammalian retina, neuronal nitric oxide synthase (NOS) is mainly localized in subpopulations of amacrine cells. One function of nitric oxide (NO) is to stimulate soluble guanylate cyclases which in turn synthesize cGMP. We used an antibody specific for cGMP to demonstrate cGMP-like immunoreactivity (cG-IR) in bovine, rat, and rabbit retinae and investigated the effects on cGMP levels of both exogenously applied NO and of endogenously released NO. We found that cGMP levels in inner and outer retina were controlled in opposite ways. In the presence of the NO-donors SNP, SIN-1 or SNAP, cG-IR was prominent in neurons of the inner retina, mainly in cone bipolar cells, some amacrine and ganglion cells. Retinae incubated in IBMX showed weak cG-IR in bipolar cells. Glutamate increased cG-IR in the inner retina, presumably by stimulating endogenous NO release, whereas NOS inhibitors or GABA and glycine decreased cG-IR in bipolar cells by reducing NO release. In somata, inner segments and spherules of rod photoreceptors the situation was reversed. cG-IR was undetectable in the presence of NO-donors or glutamate, was moderate in IBMX-treated retinae, but increased strongly in the presence of NOS inhibitors or GABA/glycine. We conclude that NO is released endogenously in the retina. In the presence of NO, cGMP levels are increased in neurons of the inner retina, but are decreased in rods.
Institut für Biologische Informationsverarbeitung 1, Forschungszentrum Jülich GmbH, Germany.
S
S
Gotzes
J
J
de Vente
F
F
Müller
D000818:Animals; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism*; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism
D009569:Nitric Oxide; D006152:Cyclic GMP