Lysophosphatidylcholine decreases locomotor activities and dopamine turnover rate in rats.
Lysophosphatidylcholine (lyso-PTC), a secondary product of S-adenosylmethionine (SAM)-dependent phosphatidylethanolamine (PTE) methylation, is a potent cytotoxin and might be involved in the pathogenesis of Parkinson's disease (PD). Our previous studies showed that the injection of SAM into the brain caused PD-like changes in rodents. Moreover, 1-methyl-4-phenylpyridinium (MPP+), a Parkinsonism-inducing agent, increased lyso-PTC formation via the stimulation of PTE methylation pathway. These results indicate a possible role of lyso-PTC in the PD-like changes seen following the injection of SAM or MPP+. In the present study, lyso-PTC was injected into the lateral ventricle of rats and locomotor activities and the biogenic amine levels were measured to evaluate the effects of lyso-PTC on the dopaminergic system. Quinacrine, a phospholipase A2 (PLA2) inhibitor, was employed to determine its protective effect on SAM-induced PD-like changes by the inhibition of lyso-PTC formation. The results showed that 1 h after the injection, 0.4 and 0.8 micromol of lyso-PTC increased striatal dopamine (DA) by 20 and 24%, decreased 3,4-dihydroxyphenylacetic acid (DOPAC) by 37 and 45% and decreased homovanilic acid (HVA) by 24 and 13%, respectively. Consequently, dopamine turnover rate, (DOPAC + HVA)/DA, was significantly reduced by 44 and 48% in the rat striatum. Meanwhile, the administration of 0.4 or 0.8 micromol of lyso-PTC decreased movement time by 52 and 63%, total distance by 44 and 48% and the number of movements by 43 and 64%, respectively. Quinacrine attenuated SAM-induced hypokinesia without affecting SAM metabolism prior to its action on rat brain. The results obtained indicate that the hypokinesia observed following the administration of lyso-PTC might be related to the decline in DA turnover in the striatum in response to lyso-PTC exposure. The present study suggests that inhibitory effects of lyso-PTC on dopaminergic neurotransmission is one of the contributing factors in SAM and MPP+-induced PD-like changes.
Lee
Eun-Sook Y
ES
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA. eunsook.lee@famu.edu
Soliman
Karam F A
KF
Charlton
Clivel G
CG
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004298:Dopamine / Q000378:metabolism*; D018476:Hypokinesia / Q000139:chemically induced / Q000503:physiopathology; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000096:biosynthesis / Q000494:pharmacology*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D050918:Phosphatidylethanolamine N-Methyltransferase; D011726:Pyridinium Compounds / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D008244:Lysophosphatidylcholines; D011726:Pyridinium Compounds; D012701:Serotonin; C026560:1-(4-methoxyphenyl)pyridinium; D012436:S-Adenosylmethionine; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D011796:Quinacrine; D004298:Dopamine