Cellular depolarization and cyclic nucleotide content in central nervous system

There is ample evidence indicating that cAMP and cGMP content in mamalian brain is markedly influenced by cellular depolarization. The relationships between the two cyclic nucleotides and the complex process of cellular depolarization, which in turn leads to extensive functional and metabolic consequences are incompletely understood, however. Much data, which are reviewed in the present chapter, suggest that cellular depolarization leads to elevation of cAMP and cGMP levels by two different and unrelated mechanisms. With regard to cAMP, it seems reasonable to conclude that cellular depolarization in CNS causes a release of adenosine, and it is the subsequent action of this substance which accounts for a portion of the elevation of cAMP levels. At present, one cannot ascertain whether or not other factors contribute to the increase of cAMP content resulting from cellular depolarization. It is probable that it is not cellular depolarization, per se, but the influx of Ca2+ into intracellular spaces caused by cellular depolarization which increases the content of cGMP. The specific effects of Ca2+, Mg2+, and other divalent cations on the cGMP response suggest a close relationship between the cyclic nucleotide and some process associated with release of one or more yet undefined neurotransmitters. Wether the involvement is in presynaptic or postsynaptic mechanisms also remains to be determined.