[Background] cAMP is produced from ATP by adenylylcyclase. Despite various G-protein coupled receptor (GPCR) signals share cAMP as second messenger, physiologicaleffects of stimulation may not be identical amongreceptors. In addition, the role of cAMP in developing apoptosis is not well understood in neuronal cells, especially during development. [Method] We first examinedthe effects of stimulating two GPCR on neuronal cell apoptosis using neonatal striatal neurons. Then, weinvestigated developmental changes of such effects in striatal neurons obtained from 2 week old mice by a newly developed culture technique in our laboratory. Cultured striatal cells were incubated with isoproterenol or dopamine, then, apoptosis was evaluated. [Result] In neonatal neurons, neither isoproterenol nor dopamine stimulation induced apoptosis. In contrast, in neuronsfrom 2 week old mice, TUNEL staining and DNA fragmentation ELISA revealed that dopaminergic receptor stimulation significantly increased the number of apoptotic cells.Western blot analysis revealed that only isoproterenol stimulation increased phosphorylation of Akt and MAP kinase. In contrast, both isoproterenol and dopamine stimulation increased cAMP. Accordingly, only dopamine stimulation induced cellular apoptosis while isoproterenoldid not, presumably due to cytoprotective effect through Akt and/or MAP kinase activation. [Conclusion] The role of cAMP in developing neuronal apoptosis differs among GPCRas well as in developmental stages. [J Physiol Sci. 2006;56 Suppl:S69]
