Intracerebroventricular antisense to inositol monophosphatase-1 reduces enzyme activity but does not affect Li-sensitive behavior.
Inositol monophosphatase (IMPase) inhibition is a hypothesized mechanism of action of lithium (Li). To test this hypothesis, the authors used the approach of antisense administration. Three days of an intracerebroventricular (icv) administration of 5 microg/20 microl 3'-phosphorothioated IMPA-1 antisense oligonucleotide sequence resulted in 20% reduction of rat periventricular IMPase activity. Li potentiates pilocarpine-induced seizures, because inhibition of IMPase leads to reduction in brain inositol levels. However, antisense-induced reduction in IMPase activity was not followed by seizures induced by subconvulsive pilocarpine doses.
Shamir
Alon
A
Stanley Foundation Research Center and Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Shaltiel
Galit
G
Agam
Galila
G
D000818:Animals; D001483:Base Sequence; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009838:Oligodeoxyribonucleotides; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase