Neuron NO synthase

Three isoforms of NO synthesizing enzymes ( nitric oxide synthase (NOS)) were isolated, purified, and cloned neuronal NO synthase ( neuronal nitric oxide synthase (nNOS) or isoform (I), immunological or inducible NOS ( inducible (immunological) nitric oxide synthase (iNOS) or isoform (II), and endothelial NOS ( endothelial nitric oxide synthase (eNOS) or isoform... 

Neuronal NO synthase (nNOS) is constitutively expressed in neurons of the brain. Its activity is regulated by Ca2+ and calmodulin. Half-saturating L-arginine concentrations are around 2 pM. cDNAs encoding nNOS have been cloned from rat and human brain. The open reading frame of human nNOS consists of 4299 bp, corresponding to 1433 aa. This predicts a protein of 160 kDa, which is in accordance with the molecular mass of the purified protein. 

In addition to nitric oxide, superoxide, and peroxynitrite, NO synthases are able to generate secondary free radicals because similar to cytochrome P-450 reductase, the reductase domain can transfer an electron from the heme to a xenobiotic. Thus it has been found [158,159] that neuronal NO synthase NOS I catalyzed the formation of CH3CH(OH) radical from ethanol. It was suggested that the perferryl complex of NOS I is responsible for the formation of such secondary radicals. Miller [160] also demonstrated that 1,3-dinitrobenzene mediated the formation of superoxide by nNOS. It was proposed that the enhancement of superoxide production in the presence of 1,3-dinitrobenzene converted nNOS into peroxynitrite-produced synthase and may be a mechanism of neurotoxicity of certain nitro compounds. 

Nitric oxide and carbon monoxide. The gaseous molecules NO and CO have both been found in the brain, and neuronal NO synthase (nNOS or NOS I) has been studied intensively.844-847 NO synthases and the functions of NO and CO are discussed in Section A7 and in Chapter 18. Complexity in understanding the role of NO in the brain arises from the fact that different isoenzyme forms of NO synthase occur in three different types of cell nNOS in neurons, iNOS from microglial immune system cells, and eNOS from endothelial cells of capillary blood vessels.846 All three types of cells are so tightly intermingled in the brain that it is hard to interpret observed experimental... 

Grasemann, H. Genetics of the neuronal NO synthase (NOSl) in the etiology of bronchial asthma. Pneumologie 2001, 55, 390-395. 

Christopherson KS, Hillier BJ, Lim WA, Bredt DS. PSD-95 assembles a ternary complex with the V-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J Biol Chem 1999 274 27,467-27,473. 

Abu-Soud, H. M., Yoho, L., and Stuehr, D. J. (1994a). Calmodulin controls neuronal NO synthase by a dual mechanism Activation of intra- and interdomain electron transfer. /. Biol. Ghent. 269, 32047-32050. 

These often involve regulation of transcription. As mentioned in Chapter 18, Section F,2, many of the effects of NO are a resulf of activation of soluble gua-nylate cyclase (p. 561). In the endothelium other hormones, such as the endothelins (p. 1750), atrial natriuretic factor, and bradykinin (Box 22-D), cooperate in the regulation of NO synthase. Neuronal NO synthase fimctions in the brain in olfaction and in formation of memory. In the peripheral system it mediates penile erection and plays a variety of roles in the enteric nervous system. Neuronal NO synthase is often localized to synaptic regions by binding to tissue-specific proteins. NO may also regulafe cellular respiration by inhibition of cytochrome c oxidase. ... 

Gozal D, Gozal E. Episodic hypoxia enhances late hypoxic ventilation in developing rat putative role of neuronal NO synthase. Am J Physiol 1999 276 R17-R22. 

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