VASOACTIVE-INTESTINAL-PEPTIDE REGULATES EXTRACELLULAR ADENOSINE LEVELS IN RAT CORTICAL CULTURES

Adenosine is an important inhibitory neuromodulator in the cerebral co rtex, yet it remains unclear how extracellular adenosine concentration s are regulated. Recently, it has been shown that P-adrenergic recepto r stimulation in rat cortical cultures causes the accumulation of extr acellular adenosine derived by enzymatic hydrolysis from adenosine cyc lic monophosphate (cAMP) transported into the extracellular space. In this study we show that vasoactive intestinal peptide (VIP), in additi on to activating adenylyl cyclase and promoting the accumulation of in tracellular cAMP in rat cortical cultures, also causes transport of cA MP and accumulation of extracellular adenosine. We further show that t he extracellular accumulation of adenosine in response to VIP can be b locked by inhibition of cAMP transport, cyclic nucleotide phosphodiest erase activity, and 5'-nucleotidase, indicating that extracellular cAM P is the source of the adenosine, Cyclic AMP transport may be a genera l mechanism by which a variety of neuromodulators that act upon recept ors coupled to adenylyl cyclase might regulate extracellular adenosine levels and thereby inhibitory tone in the cerebral cortex.