Nitric oxide synthase inhibited by audouine in the rat brain.
Nitric oxide synthase (NOS) synthesizes nitric oxide (NO) from L-arginine (Arg) which has a guanidino group in its molecule. Audouine, a derivative of Arg, is the diguanidino compound. In this study, the effects of audouine on rat brain NOS activity were investigated by measuring nitrite and nitrate formation. Audouine inhibited NOS activity in a competitive (Ki = 2.10 microM) and partially uncompetitive (Ki = 49.7 microM) manner. Audouine is not substituted at the guanidino nitrogen, in contrast to most previously reported NOS inhibitors which were synthesized by substituting the guanidino nitrogen of Arg. Audouine is a novel inhibitor of NOS and should be useful for investigating the chemical nature of NOS and the roles of NO in the central nervous system.
Asahara
H
H
Department of Orthopaedic Surgery, Okayama University Medical School, Japan.
Kabuto
H
H
Yokoi
I
I
Habu
H
H
Mori
A
A
Inoue
H
H
D000594:Amino Acid Oxidoreductases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001645:Biguanides / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley
D001645:Biguanides; D003292:Convulsants; C033461:audouine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases