Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin (5HT) modulates the development and plasticity of its innervation areas in the central nervous system (CNS). Astrocytic 5HT(1A) receptors are involved in the plastic phenomena by releasing the astroglial-derived neurotrophic factor S-100beta. Several facts have demonstrated that nitric oxide (NO) and the nitric oxide synthase enzyme (NOS) may also be involved in this neuroglial interaction: (i) NO, S-100beta and 5HT are involved in CNS plasticity; (ii) micromolar S-100beta concentration stimulates inducible-NOS (iNOS) expression; (iii) neuronal NOS (nNOS) immunoreactive neurons are functionally and morphologically related to the serotoninergic neurons; (iv) monoamines level, including 5HT, can be modulated by NO release. We have already shown that 5HT depletion increases astroglial S-100beta immunoreactivity, induces neuronal cytoskeletal alterations and produces an astroglial reaction, while once 5HT level is recovered, a sprouting phenomenon occurs [Brain Res. 883 (2000) 1-14]. To further characterize the relationship among nNOS, iNOS and 5HT we have analyzed nNOS and iNOS expression in the CNS after 5HT depletion induced by parachlorophenylalanine (PCPA) treatment. Studies were performed immediately after ending the PCPA treatment and during a recovery period of 35 days. Areas densely innervated by 5HT fibers were studied by means of nNOS and iNOS immunoreactivity as well as NADPH diaphorase (NADPHd) staining. All parameters were quantified by computer-assisted image analysis. Increased nNOS immunoreactivity in striatum and hippocampus as well as increased NADPHd reactivity in the striatum, hippocampus and parietal cortex were found after PCPA treatment. The iNOS immunoreactivity in the corpus callosum increased 14 and 35 days after the end of PCPA treatment. These findings showed that nNOS immunoreactivity and NADPHd activity increased immediately after 5HT depletion evidencing a close functional interaction between nitrergic and serotoninergic systems. However, iNOS immunoreactivity increased when 5HT levels were normalized, which could indicate one of the biological responses to S-100beta release.
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PMID:Neuronal and inducible nitric oxide synthase immunoreactivity following serotonin depletion. 1246 35

Nitric oxide (NO) is a diffusible messenger molecule produced primarily by neuronal nitric oxide synthase (nNOS) in the central nervous system. Both nNOS expression and NO production are regulated by calcium ions. Leaner and tottering mice carry a mutation in the pore forming subunit (alpha1A) of P/Q-type voltage-gated calcium ion channels, which decreases calcium ion current through the affected channels and disrupts calcium homeostasis. We have previously shown that nNOS expression is altered in adult leaner and tottering cerebella. In addition, leaner and tottering mice have been shown to have abnormal cerebellar granule cell-Purkinje cell synapses and leaner cerebellar granule cells undergo abnormal apoptosis during early postnatal development. Since NO production has been linked to several developmental roles including neuronal cell death, synaptogenesis and neuronal cell survival, our objective was to evaluate the expression of nNOS in developing leaner and tottering cerebella. Our results show that nNOS is differentially expressed in leaner and tottering cerebella compared to wild type cerebella and compared to each other. In whole cerebella, Western blotting revealed a significant increase in nNOS expression at postnatal day 12 in tottering but not leaner or wild type cerebella. At the cellular level the NADPH-diaphorase marker for nNOS revealed a significant increase in nNOS expression in basket cell interneurons in both mutant mice. nNOS expression in granule cells in the internal granule cell layer in tottering mice was increased at P12, while granule cells of leaner mice exhibited decreased nNOS expression at P20. The changes in nNOS expression at P12 did not correlate with a change in overall NO production, but rather maintained wild type NO concentrations. These findings suggest that changes in nNOS expression in the leaner and tottering cerebella are compensatory in nature with NO most likely functioning as a calcium-regulated neuroprotective/neurotrophic factor in postnatal cerebellar development.
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PMID:Developmental expression of neuronal nitric oxide synthase in P/Q-type voltage-gated calcium ion channel mutant mice, leaner and tottering. 1635 45