Quinacrine abolishes increases in cytoplasmic phospholipase A2 mRNA levels in the rat hippocampus after kainate-induced neuronal injury.
The present investigation was carried out to study the possible effects of quinacrine in modulating cytoplasmic phospholipase A(2) (cPLA(2)) mRNA levels in rat hippocampus after kainate treatment. Injections of kainate into the right lateral ventricle resulted in significant increases in cPLA(2) mRNA levels in the hippocampus, at 3 days and 7 days after injection. The elevation in cPLA(2) mRNA levels is consistent with previous observations of increased cPLA(2) immunoreactivity in degenerating neurons and astrocytes at these times. Rats that received once daily intraperitoneal injections of quinacrine (5 mg/kg) after the intracerebroventricular kainate injections showed almost complete attenuation of increased cPLA(2) expression, at both 3 and 7 days after kainate injection. These results show that in addition to its well-known effect of inhibition of PLA(2) activity, quinacrine could also inhibit cPLA(2) expression, and further supports a role for PLA(2) in kainate-induced neuronal injury.
Ong
Wei-Yi
WY
Department of Anatomy, National University of Singapore, Singapore 119260. antongwy@nus.edu.sg
Lu
Xin-Rong
XR
Ong
Benjamin Kian-Chung
BK
Horrocks
Lloyd A
LA
Farooqui
Akhlaq A
AA
Lim
Sai-Kiang
SK
D000818:Animals; D015152:Blotting, Northern; D003593:Cytoplasm; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007839:Functional Laterality; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010741:Phospholipases A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014305:Triose-Phosphate Isomerase / Q000187:drug effects / Q000235:genetics
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D010741:Phospholipases A; D054467:Phospholipases A2; D014305:Triose-Phosphate Isomerase; D011796:Quinacrine; D007608:Kainic Acid