Nitric oxide

Abstract

Nitric oxide (NO) is a gaseous chemical transmitter that is produced from the amino acid L-arginine by the members of the NO synthase (NOS) family of proteins. NO is involved in several important functions in the CNS and peripheral nervous system (PNS), including modulation of neurotransmission and regulation of local blood flow and immune responses. NO interacts with intracellular targets to trigger several signal transduction pathways. In the CNS, NO participates in synaptic modulation and plasticity, control of sleep, body temperature, and neurosecretion. In the PNS, NO mediates vasodilation and relaxation of the visceral smooth muscle. However, when produced in excess and in the setting of oxidative stress, NO becomes toxic, leading to formation of reactive nitrogen species (RNS), which cause cellular damage. These neurotoxic effects of NO derivatives may be involved in the pathogenesis of cerebral ischemia, inflammation, neoplasia, and neurodegenerative disorders. There are several comprehensive reviews on the physiologic and pathophysiologic roles of NO in the nervous system. 1-12 NITRIC OXIDE SYNTHASES Catalytic activity.The NOS family of enzymes catalyzes the oxidation of L-arginine to form L-citrulline and NO (figure 1). NOS is a dimeric enzyme; each monomer is composed of 2 distinct catalytic domains, an amino (NH2)-terminal oxygenase domain and a carboxy (COOH)-terminal reductase domain. The oxygenase domain is the binding site for heme, oxygen (O 2 ), tetrahydrobiopterin (BH4), and L-arginine; the reductase domain binds flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and reduced nicotinamide-adenine dinucleotide phosphate (NADPH). The catalytic mechanism involves flavin-mediated electron transport from NADPH to the heme center, where O 2 is reduced and incorporated into the guanidine nitrogen of L-arginine, producing NO and L-citrulline.

Moisture and mydriasis

“…Exogenous nitric oxide likely acts via production of cyclic guanosine monophosphate (GMP) within smooth muscle of the iris sphincter, with subsequent activation of protein kinase G and inhibition of intracellular calcium release, leading to smooth muscle relaxation and pupillary dilatation 2. Nitric oxide is known to reduce intraocular pressure, as was documented in our patient, and in fact has been suggested as a possible treatment in patients with glaucoma 3.…”

Inducible nitric oxide synthase inhibition by 1400W limits pain hypersensitivity in a neuropathic pain rat model

“…Of the three isoforms of NOS (endothelial, neuronal and inducible), inducible NOS (iNOS) is the primary active isoform of NOS that is upregulated at early stages post‐injury and during chronic inflammatory processes (Conti et al., ; Gühring et al., ; Hamza, Wang, Wu, & Brahim, ). The key cells that produce NO after nerve lesion are those residing in and around the injured nerves, such as activated glial cells and infiltrated macrophages that induce prolonged iNOS transcription in response to nerve injury (Aley, McCarter, & Levine, ; Amitai, ; Benarroch, ; Bradman, Arora, Morris, & Thippeswamy, ). Nitric oxide has also been shown to mediate neuronal hyperexcitability in the chronic constriction injury pain model (Makuch, Mika, Rojewska, Zychowska, & Przewlocka, ; Mukherjee, Cinelli, Kang, & Silverman, ).…”

Nitrite Reductase Activity and Inhibition of H2S Biogenesis by Human Cystathionine ß-Synthase

“…NO regulates a wide range of physiological processes including vasorelaxation, neurotransmission and immune responses [1]–[3]. Its potency as a signaling molecule relies on its short half-life, limited diffusibility and high reactivity with heme proteins [4].…”