Inhibition by soman of NMDA-stimulated [3H]norepinephrine release from rat cortical slices, studies of non-cholinergic effect.
Effects of soman, an irreversible cholinesterase (ChE) inhibitor, on [3H]norepinephrine (NE) release evoked by N-methyl-d-aspartate (NMDA) were studied in rat brain cortical slices. Soman inhibited NMDA-stimulated [3H]NE release in a concentration-dependent manner. This effect was neither reversed by atropine, an antagonist of the muscarinic receptor, nor by d-tubocurarine, an antagonist of the nicotinic receptor. Incubation of the slices with NMDA antagonists, AP5, MK-801, ketamine or magnesium, resulted in inhibitory effects on NMDA-stimulated [3H]NE release. Soman significantly shifted the inhibition curves downward and significant interactions between these chemicals and soman were observed. Glycine potentiated the release of [3H]NE stimulated by NMDA, and soman did not alter this effect of glycine. Soman also inhibited the release of [3H]NE evoked by K+ in a concentration-dependent manner. NMDA-stimulated [3H]NE release was inhibited by tetrodotoxin (TTX), an antagonist of voltage-dependent sodium channels, and a significant interaction between soman and TTX was observed. The [3H]NE release induced by NMDA was dependent on extracellular calcium concentrations and was inhibited by nifedipine, a selective blocker of the L-type voltage-dependent calcium channels (VDCC), or cadmium, a non-specific blocker of VDCC. However, no significant interaction between the effects of soman and calcium, nifedipine, or cadmium was observed. Taken together, the results suggested that: (1) soman has a direct action at non-cholinergic sites; (2) soman may interfere with some of the regulatory sites of the NMDA receptor-ion channel complex; and (3) the voltage-dependent sodium channel, but not VDCC, may be a site of action for soman.
Tang
H W
HW
Department of Biomedicine, Division of NBC Defence, Defence Research Establishment, S-90182 Umeâ, Sweden.
Cassel
G
G
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000494:pharmacology*; D014316:Tritium
D002800:Cholinesterase Inhibitors; D003292:Convulsants; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D014316:Tritium; D016202:N-Methylaspartate; D012999:Soman; D009638:Norepinephrine