THE ROLE OF CYCLIC-AMP AS A PRECURSOR OF EXTRACELLULAR ADENOSINE IN THE RAT HIPPOCAMPUS

Extracellular adenosine 3':5'-cyclic monophosphate (cAMP) is a potenti al source of the inhibitory neuromodulator adenosine in the brain. Pre vious work has demonstrated that cAMP, which is formed intracellularly , can be transported into the extracellular space and subsequently cat abolized to adenosine. However, the physiological conditions under whi ch cAMP release might lead to adenosine formation and activation of ad enosine receptors are not well understood. In this study we demonstrat e that superfusion of hippocampal slices with cAMP or forskolin led to the formation of extracellular adenosine which activated adenosine re ceptors in a manner comparable to that seen with adenosine superfusion . In contrast, application of brief pulses of cAMP onto the cell bodie s of CA1 pyramidal neurons failed to produce an adenosine receptor-med iated response, while application of brief pulses of adenosine or AMP elicited significant responses. These data suggest that large, prolong ed increases in extracellular cAMP levels can result in the formation of extracellular adenosine and the activation of adenosine receptors, but brief increases in cAMP levels in the vicinity of individual neuro ns cannot. These findings imply that increases in cAMP levels may lead to relatively slow increases in extracellular adenosine, as opposed t o the fast, spatially restricted increases that would occur following the release of other adenine nucleotides. Published by Elsevier Scienc e Ltd.