Isoforms nitric oxide synthase

S. K., Weber, P. C., Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation, Nat. Struct. Biol. 6 (1999), p. 233-242... 

Southan, G. J., Szabo, C.. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms, Biochem. Pharmacol. 51 (1996),... 

A series of analogues of 2-iminopiperidine have been prepared and have been shown to be potent inhibitors of the human nitric oxide synthase isoforms °. The cyclopentanone oxime 346 was esterified with sodium hydroxide and benzenesulfonyl chloride and the subsequent Beckmann rearrangement afforded the 6-propylvalerolactam 348 as the major product and 3-propylvalerolactam 347 as a minor product (equation 133). The major product was converted into the intended 2-iminopiperidine 349. 

Figure 3 Schematic representation of nitric oxide synthase isoforms and cytochrome P450 reductase. Haem, heme PDZ, PDZ domain (GLGF repeats) CaM, calmodulin FMN, flavin mononucleotide FAD, flavin adenine dinucleotide (adapted from Hobbs et al., 1999).

Wattanapitayakul, S.K., Young, A.P., Bauer, J.A. Genetic variations in nitric oxide synthase isoforms, Pharmaceut. News 2000, 7, 14-20. 

Sears, C.E., Bryant, S.M., Ashley, E.A., Lygate, C.A., Rakovic, S., Wallis, H.L., Neubauer, S., Terrar, D.A., Casadei, B., 2003, Cardiac neuronal nitric oxide synthase isoform regulates myocardial contraction and calcium handling. Circ Res 92, 52-59. 

In other recent reports concerning enzymatic inhibition and receptor binding of organofullerene materials, C60 monomalonate adducts were found to selectively inactivate the neuronal nitric oxide synthase isoform in a manner completely preventable by the concurrent presence of superoxide dismutase and catalase [295]. Also two fullerene-steroid hybrids were synthesized and found to decrease both the ATP hydrolysis and Ca2+ uptake activity of SR Ca2+-ATPase while the inhibitions were concentration dependent [296]. 

Fischmann, T. O., Hruza, A., Niu, X. D., Fossetta, J. D. Lunn, C. A., Dolphin, E., Prongay, A. J., Reichert, P., Lundell, D. J., Narula, S. K. and Weber, P. C. (1999) Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation, Nature Struct. Biol. 6, 233-242. 

Morishita T, Tsutsui M, Shimokawa H, Sabanai K, Tasaki H, Suda O, Nakata S, Tanimoto A, Wang KY, Ueta Y, Sasaguri Y, Nakashima Y, Yanagihara N. Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms. Proc. Natl. Acad. Sci. U. S. A. 2005 102 10616-10621. 

Rengasamy, A., and Johns, RA. 1996. Determination of Km for oxygen of nitric oxide synthase isoforms. J Pharmacol Exp Ther 276 30-33. 

Lopez-Costa JJ, Goldstein J, Saavedra JP. 1997. Neuronal and macrophagic nitric oxide synthase isoforms distribution in normal rat retina. Neurosci Lett 232 155-158. 

Wolff, D. J., and Gribin, B. J. (1994). The inhibition of the constitutive and inducible nitric oxide synthase isoforms by indazole agents. Arch. Biochem. Biophys. 311, 300-306. 

Anandamide and 2-arachidonylglycerol can directly stimulate nitric oxide release via CBj (Stefano et al., 1996 Stefano et al., 2000). This direct stimulation of constitutive nitric oxide synthase has been shown in immunocytes, microglia, and monocytes, as well as in endothelial cells from blood vessels (Stefano et al., 2000). As constitutive nitric oxide synthase isoforms are Ca +-calmodulin dependent, an intermediate step in this pathway may be increased intracellular calcium, as described earlier. 

Wang R, Ghahary A, Shen YJ, Scott PG, Tredget EE. Human dermal fibroblasts produce nitric oxide and express both constitutive and inducible nitric oxide synthase isoforms. J Invest Dermatol 1996 106 419-427. 

Renal and vascular endothelial (eNOS) and inducible (iNOS) nitric oxide synthase isoforms were markedly upregulated in the prehypertensive (4-week-old) and adult hypertensive (12-week-old) spontaneously hypertensive rats (Vaziri et al. 1998). Compared to the Wistar-Kyoto control rats, untreated spontaneously hypertensive rats showed severe hypertension, elevated urinary NO metabolite (NO j excretion, marked upregulation of renal and vscular eNOS and iNOS proteins, normal renal function and heart weight at 9 weeks of age (Vaziri... 

Vaziri, N.D., Ding, Y., Ni, Z., 2001. Compensatory up-regulation of nitric-oxide synthase isoforms in lead-induced hypertension reversal by a superoxide dismutase-mimetic drug. J. Pharmacol. Exp. Ther. 298, 679—685. 

Gozal D, Gozal E, Gozal YM, Torres JE. Nitric oxide synthase isoforms and peripheral chemoreceptor stimulation in conscious rats. Neuroreport 1996 7 1145-1148. 

Nussler, A.K., Gansauge, S., Gansauge, R, Fischer, U., Butzer, U., Kremsner, P.G., and Beger, H.G. (1998). Overexpression of endothelium-derived nitric oxide synthase isoform 3 in the vasculature of human pancreatic tumor biopsies. Langenbecks Arch. Surg. 383(6), 474—480. 

Mendes, R.V., Martins, A.R., de Nucci, G., Murad, E, and Soares, F.A. (2(X)1). Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B-cell non-Hodgkin s lymphomas and multiple myeloma. Histopathology 39, 172-178. 

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