Nordidemnin potently inhibits inositol uptake in cultured astrocytes and dose-dependently augments lithium's proconvulsant effect in vivo.
It has been suggested that inositol uptake across the cell membrane is of importance for maintenance of the inositol pool involved in lithium's therapeutic effect in bipolar disease and in the lithium-pilocarpine seizure test in freely moving rats (measuring the latency of a normally subconvulsive concentration of pilocarpine to seizure induction in the additional presence of lithium). We have tested this hypothesis by: 1) demonstrating an extremely high potency of nordidemnin as an inhibitor of myo-inositol uptake in primary cultures of mouse astrocytes; and 2) determining the dose-response correlation of a nordidemnin-induced decrease in the latency before appearance of seizures in the lithium-pilocarpine test after intracerebroventricular injection of minute samples (10 microl) of virtually isotonic saline solution.
Wolfson
M
M
Department of Microbiology and Immunology and Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. wolfson@bgumail.bgu.ac.il
Einat
H
H
Bersudsky
Y
Y
Berkin
V
V
Belmaker
R H
RH
Hertz
L
L
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D003292:Convulsants / Q000494:pharmacology*; D047630:Depsipeptides; D004347:Drug Interactions; D007294:Inositol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D051379:Mice; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018692:Antimanic Agents; D003292:Convulsants; D047630:Depsipeptides; D010456:Peptides, Cyclic; C067388:nordidemnin B; D007294:Inositol; D018021:Lithium Chloride