Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues.

TLDR

NADPH diaphorase–positive neurons, known for resistance to neurotoxicity, co‑express nitric oxide synthase, the enzyme that produces the neuronal messenger nitric oxide. The study investigates whether neuronal NO synthase and NADPH diaphorase are identical, suggesting NO’s role in modulating neurotoxicity. Transfecting human kidney cells with NO synthase cDNA induces NADPH diaphorase staining, demonstrating a causal relationship. In brain regions such as the corpus striatum, cerebral cortex, and pedunculopontine nucleus, as well as in peripheral tissues like the retina, intestine, and adrenal medulla, NO synthase immunoreactivity perfectly colocalizes with NADPH diaphorase staining, and the enzyme accounts for all observed staining.

Abstract

NADPH diaphorase staining neurons, uniquely resistant to toxic insults and neurodegenerative disorders, have been colocalized with neurons in the brain and peripheral tissue containing nitric oxide synthase (EC 1.14.23.-), which generates nitric oxide (NO), a recently identified neuronal messenger molecule. In the corpus striatum and cerebral cortex, NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in medium to large aspiny neurons. These same neurons colocalize with somatostatin and neuropeptide Y immunoreactivity. NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in the pedunculopontine nucleus with choline acetyltransferase-containing cells and are also colocalized in amacrine cells of the inner nuclear layer and ganglion cells of the retina, myenteric plexus neurons of the intestine, and ganglion cells of the adrenal medulla. Transfection of human kidney cells with NO synthase cDNA elicits NADPH diaphorase staining. The ratio of NO synthase to NADPH diaphorase staining in the transfected cells is the same as in neurons, indicating that NO synthase fully accounts for observed NADPH staining. The identity of neuronal NO synthase and NADPH diaphorase suggests a role for NO in modulating neurotoxicity.