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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
| Content Provider | Scilit |
|---|---|
| Author | Tomimatsu, Naoko Arakawa, Yoshihiro |
| Copyright Year | 2008 |
| Description | Journal: Journal of Neurochemistry 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 signaling pathway for the possible therapeutic target of amyotrophic lateral sclerosis as glutamate excitotoxicity was suggested in sporadic amyotrophic lateral sclerosis. |
| Ending Page | 635 |
| Starting Page | 628 |
| ISSN | 2573508X |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.2008.05638.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 3 |
| Volume Number | 107 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2008-11-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Biochemistry and Molecular Biology Neurotrophic Activity Phosphodiesterase Inhibitor Pituitary Adenylate Cyclase‐activating Polypeptide |
| Content Type | Text |
| Resource Type | Article |
