The regulatory mechanisms of PACAP expression in neuronal cells

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.105-105
• Main Authors: Hashimoto, Hitoshi, Koga, Kazumi, Hagihara, Nami, Shintani, Norihito, Yamamoto, Kyohei, Tomimoto, Shuhei, Kunugi, Akiyoshi, Matsuda, Toshio, Baba, Akemichi
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)47886-4

Pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression was analyzed in PC12 cells using the luciferase reporter gene systems, RT-PCR, and Northern blot analysis. PACAP gene transcription was induced by NGF and also by PACAP. Simultaneous treatment with PACAP and NGF resulted in a synergistic transcriptional response. This synergism paralleled the PACAP mRNA levels, as determined by RT-PCR and Northern blotting. The level of PACAP mRNA peaked 3 hours after stimulation and gradually returned to basal levels by 48 hours. The ERK kinase 1/2 (MEK1/2) inhibitor PD98059 blocked the PACAP mRNA expression induced by either PACAP or NGF, but not that induced by a combination of PACAP and NGF. These results suggest that the ERK1/2 cascade is involved in PACAP and NGF.induced PACAP gene expression, although redundant signalling pathways may also be involved. In addition, NGF-induced PACAP mRNA expression was reduced to 67% by PACAP(6-38), a PACAP receptor antagonist. The present findings strengthen the role of PACAP as an autocrine regulatory factor.