Activation of Phosphoinositide Metabolism by Cholinergic Agents.
Rept. for 15 Feb 1989-14 Nov 1990
ALABAMA UNIV IN BIRMINGHAM
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The primary acute, toxic effect of cholinergic agonists in the central nervous system is the production of seizures which are often fatal. One of the major signal transducing systems in the brain activated by cholinergic agonists is the hydrolysis of phosphoinositides. This system is a major site of action of lithium which also potentiates the convulsions and death associated with administration of cholinergic agonists. Therefore, the overall goal of the project is to determine how phosphoinositide hydrolysis, as well as protein phosphorylation, is modulated, especially by excitatory amino acids which mediate many types of seizures and by an inhibitory amino acid which blocks seizures, and how these processes are affected by cholinergic agonist-induced seizures, with an emphasis on those induced by co-administrator of lithium and pilocarpine.