Cyclic 3′, 5′‐nucleotides in extracellular fluids of neural systems

The cyclic nucleotides (CN) cAMP and cGMP occur in considerable amounts in body fluids such as urine, blood and cerebrospinal fluid (CSF). Whether changes in the CN concentrations of blood and CSF reflect metabolic events within the nervous tissues is a relevant question both in terms of possible roles of CN and of clinical diagnostic purposes. Studies are reviewed which show that cAMP is released from brain slices and from intact peripheral ganglia upon stimulation by electric pulses or exposure to biogenic amines in vitro. By using a prelabeling method with 14C‐adenine evidence is presented that cAMP is released preferentially from a membrane‐associated pool functionally linked to the action of neurotransmitters. In the CSF compartment which is closely related to the extracellular space of the central nervous system, CN levels are in a dynamic equilibrium. An attempt is made to estimate the magnitude of flux rates following inhibition of efflux from the compartment. CN seem to be cleared from the CNS, at least in part, by the choroid plexuses which contain high activities of CN phosphodiesterase but also of adenylate cyclase, possibly related to their secretory and homeostatic functions. Release into and rapid removal from extracellular compartments by transport and degradation may be important means to limit the actions of CN in cells. Whether extracellular CN, in addition, have regulatory functions of their own still remains a matter of speculation.