2-2'-PYRIDYLISATOGEN, A SELECTIVE ALLOSTERIC MODULATOR OF P2 RECEPTORS, IS A SPIN-TRAPPING AGENT

2-2'Pyridylisatogen (PIT) has been reported to be a relatively selecti ve irreversible antagonist of responses to adenosine 5'-triphosphate ( ATP) in some smooth muscle preparations and to be an allosteric modula tor of responses to ATP at recombinant P2Y receptors from chick brain. PIT is also a potent inhibitor of mitochondrial oxidative phosphoryla tion. However, the compound has a unique nitrone structure, so PIT was compared with dimethyl-pyrroline-N-oxide (DMPO) as a spin trapping ag ent 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 hydrox yl radical forming an adduct which was more stable than the DMPO adduc t 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 a nion but at concentrations where DMPO trapped none. (C) 1998 Academic Press.