Inhibitory effects of lysophosphatidylcholine on the dopaminergic system.
Lysophosphatidylcholine (lyso-PTC) is formed by phospholipase A2 (PLA2) from phosphatidylcholine (PTC), that is produced through phosphatidylethanolamine (PTE) methylation. 1-Methyl-4-phenyl-pyridinium (MPP+), a Parkinson's disease (PD) inducing agent, and S-adenosylmethionine (SAM), a biological methyl donor, increase lyso-PTC formation and both induce PD-like changes in animal models. In the current study, we investigated the effect of lyso-PTC on the dopaminergic system to determine the modulating role of lyso-PTC in dopaminergic neurotransmission. The results of these experiments show that lyso-PTC has a remarkable inhibitory effect on dopamine D1 and D2 receptor binding activities in the striatal membrane prepared from Sprague-Dawley rats. Lyso-PTC decreased the Bmax values of both D1 and D2 receptor binding activities. The Kd values for D1 and D2 receptors were not changed, but lyso-PTC also inhibited dopamine transporter and decreased striatal dopamine turnover rate. MPP+ showed similar, but less potent effects. The current studies suggest that lyso-PTC significantly impair the dopaminergic system and might play a role in MPP+ and SAM induced PD-like changes through its inhibitory effects on dopaminergic neurotransmission.
Lee
Eun-Sook Y
ES
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida 32307, USA. eunsook.lee@famu.edu
Chen
Hongtao
H
Shepherd
Kennie R
KR
Lamango
Nazarius S
NS
Soliman
Karam F A
KF
Charlton
Clivel G
CG
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology
D018492:Dopamine Antagonists; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine