PT  - JOURNAL ARTICLE
AU  - J. A. FERRENDELLI
AU  - D. A. KINSCHERF
AU  - M. M. CHANG
TI  - Regulation of Levels of Guanosine Cyclic 3',5'-Monophosphate in the Central Nervous System: Effects of Depolarizing Agents
DP  - 1973 Jul 01
TA  - Molecular Pharmacology
PG  - 445--454
VI  - 9
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/9/4/445.short
4100  - http://molpharm.aspetjournals.org/content/9/4/445.full
SO  - Mol Pharmacol1973 Jul 01; 9
AB  - Veratridine, ouabain, and K+, agents which are known to produce depolarization of nervous tissue, increase the levels of cyclic GMP in incubated slices of mouse cerebellum. Each of the agents acts in a dose-related fashion, and each produces a maximum elevation of cyclic GMP levels which is 25-30 times control levels. The effects of all three agents on cyclic GMP accumulation are dependent on Ca++. Atropine does not block and acetylcholine does not mimic the effect of the depolarizing agents. High concentrations of K+, in addition to increasing levels of cyclic GMP, also greatly increase levels of cyclic AMP in slices of mouse cerebellum. However, the rate of accumulation of cyclic AMP is more rapid than that of cyclic GMP, induction of cyclic AMP accumulation requires higher concentrations of K+, and theophylline markedly attenuates the accumulation of cyclic AMP produced by K+ but not that of cyclic GMP. Furthermore, adenosine produces an accumulation of cyclic AMP but not of cyclic GMP. These data indicate that the effects of depolarization on cyclic AMP and cyclic GMP levels in nervous tissue are mediated by separate mechanisms. The effects of depolarization on cyclic nucleotide levels in cerebral cortex are different from those in cerebellum. In cerebral cortex slices, high concentrations of K+ produce a much smaller accumulation of cyclic GMP than in cerebellum slices, whereas the K+-induced accumulation of cyclic AMP in cerebral cortex is greater than that in cerebellum.