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Forskolin evokes extracellular adenosine accumulation in rat cortical cultures
1Department of Neurology and Program in Neuroscience, Children's Hospital, Boston, MA 02115, USA.
Abstract:
In this study, the effect on extracellular adenosine concentration of direct activation of adenylyl cyclase by forskolin was investigated using rat cortical cultures. Forskolin evoked intracellular and extracellular cAMP accumulation as well as extracellular adenosine accumulation. The accumulation of adenosine in response to forskolin could be blocked by the cyclic nucleotide phosphodiesterase inhibitor 4-[(3-butoxy-4-methoxyphenyl)methyl]-2-imidazolidinone (RO 20-1724; 180 microM), but not isobutylmethylxanthine (100 microM). The accumulation of adenosine in response to forskolin could be blocked by the 5'-ectonucleotidase inhibitor guanosine 5'-monophosphate. These results demonstrate that forskolin can increase extracellular adenosine levels, and that this adenosine is ultimately derived from cAMP.