Acute effects of Soman, Sarin, and Tabun on cyclic nucleotide metabolism in rat striatum

Abstract

Rats were injected sc with 120 μg/kg Soman, 120 μg/kg Sarin or 240 μg/kg Tabun. At 15 min, 2 h, or 6 h after administration, animals were decapitated along with saline‐treated controls, and striatal activities of nucleotide cyclases and phosphodiesterases and striatal cyclic nucleotide levels were determined. All three agents had two similar effects on rat striatal cyclic nucleotide systems: (1) they all increased cyclic GMP levels 15 min after their administration, and (2) they all decreased guanylate cyclase activity 2 h after administration. There were also some different effects elicited by these three organophosphorus compounds. Different effects of Soman and Sarin seem to be mainly due to their different potencies, which in turn influence the time course of their actions. Tabun is quite different from Soman and Sarin in several respects: (1) it rarely causes convulsions at sub‐lethal doses, (2) it has no effects on striatal cyclic AMP levels, and (3) it affects enzyme activities 6 h after its administration. These differences may be due to the presence of cyanide instead of fluoride in its structure: i.e., this may be responsible for the different effects of Tabun on striatal cyclic nucleotide systems, and perhaps other biochemical effects. These results also indicate that other neurotransmitter systems, in addition to the cholinergic system, may be involved in organophosphate‐induced toxicity.