Nepveu F, Souchard J P, Rolland Y, Dorey G, Spedding M
Université Paul Sabatier, Faculté des Science Pharmaceutiques, Toulouse, France.
Biochem Biophys Res Commun. 1998 Jan 14;242(2):272-6. doi: 10.1006/bbrc.1997.7949.
2-2'-Pyridylisatogen (PIT) has been reported to be a relatively selective irreversible antagonist of responses to adenosine 5'-triphosphate (ATP) in some smooth muscle preparations and to be an allosteric modulator of responses to ATP at recombinant P2Y receptors from chick brain. PIT is also a potent inhibitor of mitochondrial oxidative phosphorylation. However, the compound has a unique nitrone structure, so PIT was compared with dimethyl-pyrroline-N-oxide (DMPO) as a spin trapping agent for superoxide and hydroxyl radicals using electron spin resonance (ESR). PIT was found to be a potent spin trapper of both hydroxyl and superoxide radicals. PIT was more potent than DMPO to trap the hydroxyl radical forming an adduct which was more stable than the DMPO adduct in aqueous media. PIT was an effective spin trap of hydroxyl radical in aqueous buffer at pH 7.4. PIT more slowly trapped the superoxide anion but at concentrations where DMPO trapped none.
据报道，2-2'-吡啶异吲哚酮（PIT）在一些平滑肌制剂中是对腺苷5'-三磷酸（ATP）反应的相对选择性不可逆拮抗剂，并且在鸡脑重组P2Y受体上是对ATP反应的变构调节剂。PIT还是线粒体氧化磷酸化的有效抑制剂。然而，该化合物具有独特的硝酮结构，因此使用电子自旋共振（ESR）将PIT与二甲基-吡咯啉-N-氧化物（DMPO）作为超氧化物和羟基自由基的自旋捕获剂进行了比较。发现PIT是羟基和超氧化物自由基的有效自旋捕获剂。PIT捕获羟基自由基比DMPO更有效，形成的加合物在水性介质中比DMPO加合物更稳定。PIT在pH 7.4的水性缓冲液中是羟基自由基的有效自旋捕获剂。PIT捕获超氧阴离子的速度较慢，但在DMPO无法捕获的浓度下可以捕获。
