| 18270316 |
Matsumura N, Kikuchi-Utsumi K, Nakaki T: Activities of 7-nitroindazole and 1-(2-(trifluoromethylphenyl)-imidazole independent of neuronal nitric-oxide synthase inhibition. J Pharmacol Exp Ther. 2008 May;325(2):357-62. Epub 2008 Feb 12.
7-Nitroindazole (NI) is a widely used inhibitor of neuronal nitricoxide synthase (nNOS) used to study the role of the neuronal NO pathway in the nervous system. 7-NI prevents convulsions, including 2-amino-4-methylphosphinobutyric acid (glufosinate)-induced convulsions, in experimental models. Herein, we examined nNOS involvement in glufosinate-induced convulsions and the specificity of 7-NI for nNOS. Another nNOS inhibitor, 1-[2-(trifluoromethyl) phenyl] imidazole (TRIM), inhibited NOS activity in vivo, and it prevented glufosinate-induced convulsions. In contrast, an endothelial NOS inhibitor, N (5)-(1-iminoethyl)-l-ornithine, inhibited NOS activity in vivo, but it did not prevent the convulsions. These results suggest the involvement of nNOS in glufosinate-induced convulsions. However, a nonspecific NOS inhibitor, N (omega)-nitro-l-arginine methyl ester, inhibited NOS activity in vivo, but it failed to prevent glufosinate-induced convulsions. 6-NI and indazole, which did not inhibit NOS activity in vivo, suppressed glufosinate-induced convulsions. Moreover, glufosinate elicited convulsions in nNOS-deficient mice. These results suggest the anticonvulsant effects of 7-NI and TRIM on glufosinate-induced convulsions do not involve nNOS inhibition, instead possibly being related to an undefined property of nitrogen-containing chemical structures. |
49(0,1,4,4) |