Endogenous oxidized indoles share inhibitory potency against [3H]isatin binding in rat brain.
Isatin is an endogenous oxidized indole that influences a range of processes in vivo and in vitro. It has a distinct and discontinuous distribution in the brain and [3H]isatin binding sites are widely distributed in rat brain sections. The highest labelling is found in hypothalamic nuclei and in the cortex, hippocampus, and cerebellum (Crumeyrolle-Arias et al., 2003). However, the properties of most isatin binding sites and their physiological ligands remain unknown. In the present study the effects of three endogenous oxidized indoles (oxindole, 5-hyxdoxyoxindole, and isatin) on [3H]isatin binding were investigated in rat brain sections. In most regions cold isatin (0.2 mM) significantly reduced [3H]isatin binding. In addition to isatin, the other endogenous oxidized indoles, 5-hydroxyoxindole and oxindole were effective in displacing [3H]isatin. Total irreversible inhibition of monoamine oxidases caused inhibition of specific [3H]isatin binding in 7 of 10 brain region studied. This was accompanied by altered sensitivity of [3H]isatin binding to these indoles, including regions where a decrease of specific binding was not detected. The combinations of the three oxidized indoles produced two clear effects: augmentation (potentiation) and attenuation (blockade) of inhibitory activity compared with the independent effects of these compounds. The different effects of oxidized indoles and their combinations (isatin + 5-hydroxyoxindole and isatin + oxindole) in various brain regions therefore suggest an interaction of [(3H]isatin with different and multiple isatin-binding sites, which exhibit different sensitivity to endogenous oxidizing indoles.
Crumeyrolle-Arias
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M
INSERM U513, UFR Médecine, Université Paris 12, Créteil, France. Michele.Crumeyrolle@creteil.inserm.fr
Medvedev
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A
Cardona
A
A
Tournaire
M C
MC
Glover
V
V
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D007510:Isatin / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000078183:Oxindoles; D051381:Rats; D017208:Rats, Wistar
C484744:5-hydroxyoxindole; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D000078183:Oxindoles; C022960:2-oxindole; D007510:Isatin