Acute effects of soman, sarin, and tabun on microsomal and cytosolic components of the calmodulin system in rat striatum.
Two hours after administration of Soman (120 micrograms/kg, s.c.), Sarin (150 micrograms/kg, s.c.), or Tabun (240 micrograms/kg, s.c.), microsomes and cytosol were prepared from rat striata. Microsomal and cytosolic calmodulin (CaM) levels, microsomal adenylate and guanylate cyclase activities, protein kinase activities, and Ca2+ + Mg2+-ATPase activities were determined while cytosolic phosphodiesterase (PDE) activities were determined. CaM levels in both cell fractions were significantly increased by Soman and Sarin. Cyclic AMP-PDE and adenylate cyclase activities were decreased by Soman and Sarin. All three agents decreased activities of cyclic GMP-PDE and guanylate cyclase. Sarin and Tabun administration caused significant increases in microsomal protein kinase activity and none of the agents affected activity of divalent cation ATPases. The intensity of effects of the three organophosphates roughly paralleled their observed neurotoxic potencies. The results indicate that components of the CaM system are implicated as either causative or adaptive changes induced by these agents.
Hoskins
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Liu
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Ho
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D010755:Organophosphates / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012524:Sarin / Q000494:pharmacology*; D012999:Soman / Q000494:pharmacology*
D002147:Calmodulin; D010755:Organophosphates; D009943:Organophosphorus Compounds; D012999:Soman; D012524:Sarin; D011494:Protein Kinases; D010727:Phosphoric Diester Hydrolases; D017301:Ca(2+) Mg(2+)-ATPase; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000252:Calcium-Transporting ATPases; C009374:tabun