Dopaminergic denervation enhances susceptibility to hydroxyl radicals in rat neostriatum.
To determine if greater amounts of hydroxyl radical (*OH) are formed by dopamine (DA) denervation and treatment with L-dihydroxyphenylalanine (L-DOPA), the neostriatum was DA denervated (99% reduction in DA content) by 6-hydroxydopamine treatment (134microg icv, desipramine pretreatment) of neonatal rats. At 10 weeks the peripherally restricted dopa decarboxylase inhibitor carbidopa (12.5mg/kg i.p.) was administered 30min before vehicle, L-DOPA (60mg/kg i.p.), or the known generator of reactive oxygen species, 6-hydroxydopa (6-OHDOPA) (60mg/kg i.p.); and this was followed 30min later (and 15 min before termination) by the spin trap, salicylic acid (8micromoles icv). By means of a high performance liquid chromatographic method with electrochemical detection, we found a 4-fold increase in the non-enzymatically formed spin trap product, 2,3-dihydroxybenzoic acid (2,3-DHBA), with neither L-DOPA nor 6-OHDOPA having an effect on 2,3-DHBA content of the neostriatum. Basal content of 2,5-DHBA, the enzymatically formed spin trap product, was 4-fold higher vs. 2,3-DHBA in the neostriatum of untreated rats, while L-DOPA and 6-OHDOPA each reduced formation of 2,5-DHBA. We conclude that DA innervation normally suppresses *OH formation, and that the antiparkinsonian drug L-DOPA has no effect (2,3-DHBA) or slightly reduces (2,5-DHBA) *OH formation in the neostriatum, probably by virtue of its bathing the system of newly formed *OH.
Kostrzewa
R M
RM
Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA. Kostrezew@ETSU.Edu
Kostrzewa
J P
JP
Brus
R
R
D000818:Animals; D002230:Carbidopa / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D003714:Denervation; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005841:Gentisates; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D020156:Salicylic Acid / Q000008:administration & dosage; D012701:Serotonin / Q000378:metabolism
D005841:Gentisates; D062385:Hydroxybenzoates; C001388:6-hydroxydopa; D012701:Serotonin; D017665:Hydroxyl Radical; D004295:Dihydroxyphenylalanine; C009135:2,3-dihydroxybenzoic acid; D002230:Carbidopa; D020156:Salicylic Acid; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine