Activation of phosphoinositide hydrolysis in rat cortical slices by guanine nucleotides and sodium fluoride.
The role of guanine nucleotide binding protein in phosphoinositide metabolism in the central nervous system was studied in rat brain cortical slices prelabelled with [(3)H]inositol. Addition of guanosine triphosphate and its analogs increased the accumulation of [(3)H]inositol monophosphate in the presence of lithium chloride (10 mM). These stimulatory effects were specific for the guanine moiety as no measurable effect was observed with other adenine nucleotides. Forskolin and dibutyryl cyclic adenosine monophosphate did not affect the phosphoinositide hydrolysis, indicating that the guanine nucleotide effect on phosphoinositide hydrolysis is not mediated by the activation of the adenylate cyclase system. Sodium fluoride, a direct activator of guanine nucleotide binding protein, also increased the accumulation of [(3)H]inositol monophosphate in a concentration-dependent manner, and the observed effect was specific for fluoride ion. Taken together, the results support and extend earlier suggestions that a putative guanine nucleotide binding protein is involved in phosphoinositide metabolism in the central nervous system.
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Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, Toronto, Ontario Canada M5T 1R8.
Chiu
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Warsh
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