We investigated the role of DARPP-32 in mediating changes in phosphorylation after sarin exposure. Wild type mice and mice bearing a targeted disruption of the gene for DARPP-32 were exposed to sarin; levels of brain phosphoproteins were measured. Mice receiving 1.0 x LD50 dose of sarin displayed motor convulsions. No significant change in phosphorylation level of T75 DARPP-32 was observed in brains of wild type mice. Also, no significant changes ...
Organophosphorous (OP) nerve agents, such as sarin, exert acute effects by inhibiting acetylcholinesterase in the central and peripheral nervous systems, which results in accumulation of acetylcholine and, in turn, an excessive stimulation of nicotinic and muscarinic receptors. Preliminary evidence using diverse OPs indicates that the DARPP-32/PP-1 signaling pathway is activated by nicotinic receptor stimulation. We investigated whether treatment of whole animals with sarin activated the DARPP-32/PP-1 signaling cascade. Both a ...