Convulsions and cerebral inositol-1-phosphate levels in rats treated with diisopropyl fluorophosphate.
In order to examine the relationship of organophosphate-induced cholinergic stimulation to phosphoinositide (PI) hydrolysis in the brain, diisopropyl fluorophosphate (DFP; 1.3 or 1.5 mg/kg subcutaneously) was given to rats pretreated with saline or LiCl (5 meq/kg subcutaneously). Behaviour was monitored 60 min. after the administration of DFP, and inositol-1-phosphate (IP1), an intermediate in PI metabolism, was measured in the brain DFP alone caused tremors, whereas with LiCl pretreatment, DFP caused tremors and tonic-clonic convulsions. DFP alone did not increase IP1 above control levels. LiCl alone elevated IP1 2-5 fold but did not alter rat behavior. With LiCl pretreatment, DFP caused IP1 to increase 2-4 fold above LiCl control values in convulsing rats. LiCl increased the potential of DFP to induce convulsions and greatly amplified IP1 elevations induced by DFP.
Savolainen
K M
KM
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Terry
J B
JB
Nelson
S R
SR
Samson
F E
FE
Pazdernik
T L
TL
D000818:Animals; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry; D003292:Convulsants; D007295:Inositol Phosphates / Q000378:metabolism*; D007531:Isoflurophate / Q000633:toxicity*; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*
D003292:Convulsants; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D007531:Isoflurophate; C002647:inositol 1-phosphate