Survival-promoting activity of pituitary adenylate cyclase-activating polypeptide in the presence of phosphodiesterase inhibitors on rat motoneurons in culture: cAMP-protein kinase A-mediated survival

Journal of Neurochemistry
Naoko Tomimatsu, Yoshihiro Arakawa

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to be neurotrophic or neuroprotective in various neurons in culture. It is expressed in spinal motoneurons in vivo and its expression is increased markedly after axotomy, suggesting a neuroprotective role via an autocrine mechanism. However, neurotrophic activity of PACAP has not been reported for motoneurons. In the present study, we investigated the effects of PACAP on rat motoneurons in culture. In the presence of a phosphodiesterase inhibitor, PACAP showed significant neurotrophic activity at concentrations as low as 0.01 nM. Previously, we found that glutamate was excitotoxic to motoneurons even in the presence of brain-derived neurotrophic factor, which is neurotrophic for motoneurons. PACAP with a phosphodiesterase inhibitor protected motoneurons against this excitotoxicity. The activity of PACAP was inhibited by the protein kinase A inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride, as was the case with the activity of forskolin, suggesting downstream involvement of a cAMP-protein kinase A signaling pathway. The present results may suggest a physiological role of PACAP in vivo, and implicate the PACAP-cAMP sign...Continue Reading

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Citations

May 21, 2013·Cell Biochemistry and Biophysics·He HuangMaria E Figueiredo-Pereira
Oct 7, 2011·Journal of Molecular Neuroscience : MN·Yvonne HolighausLee E Eiden
Apr 26, 2020·International Journal of Molecular Sciences·Agata Grazia D'AmicoVelia D'Agata
Aug 29, 2020·Journal of Molecular Neuroscience : MN·Vladimir A Martínez-RojasCarlo Musio
Aug 28, 2020·Frontiers in Neuroscience·Grazia MaugeriVelia D'Agata

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