Effect of the adenosine A2A receptor antagonist 8-(3-chlorostyryl)caffeine on L-DOPA biotransformation in rat striatum.
In the present study, we investigated effects of the new selective adenosine A2A receptor antagonist 8-(3-chlorostyryl)caffeine (CSC) on L-DOPA-induced dopamine (DA) release in the striatum of intact and reserpine-treated rats. CSC given in a pharmacologically effective dose of 5 mg/kg i.p. significantly increased striatal DA release after joint administration of L-DOPA (100 mg/kg, i.p.) and benserazide (50 mg/kg, i.p.) to intact and reserpine (2.5 mg/kg, s.c.)-injected rats. CSC did not change the elevated level of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in intact rats, but raised it in DA-depleted animals. The availability of exogenous L-DOPA in the extracellular space was similar and equally increased by CSC in both intact and reserpinized rats. Our results suggest that the observed effects may be mediated by striatal adenosine A2A receptors, and are probably related to the CSC action on DA metabolism and the increased transport of exogenous L-DOPA into the brain. These observations might be of relevance, considering the use of selective A2A antagonists as potential supplements to L-DOPA therapy of Parkinson's disease.
Gołembiowska
Krystyna
K
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. nfgolemb@cyf-kr.edu.pl
Dziubina
Anna
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D018759:Adrenergic Uptake Inhibitors; D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; D007980:Levodopa; D001545:Benserazide; D012110:Reserpine; D004298:Dopamine; D006719:Homovanillic Acid