title: Pituitary adenylate cyclase-activating polypeptide (PACAP) is an upstream regulator of prodynorphin mRNA expression in neurons.
abstract: Although dynorphins are widely involved in the control of not only nociceptive neurotransmission but also a variety of brain functions such as memory and emotion, no natural regulator for inducing the mRNA expression of prodynorphin (Pdyn), a precursor protein of dynorphins, is known. Using primary cultures of rat cortical neurons, we found that pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon neuropeptide family, markedly induces Pdyn mRNA expression. PACAP was much more effective than VIP, indicating a major role for PAC1 in the PACAP-induced Pdyn mRNA expression. The increase in Pdyn mRNA expression was independent of de novo protein synthesis. Administration of forskolin, an activator for adenylate cyclase/protein kinase A (PKA), but not TPA, an activator for protein kinase C (PKC), induced Pdyn mRNA expression, suggesting a major role for PKA. The involvement of PKA was supported by the inhibition of PACAP-induced Pdyn mRNA expression upon addition of H89, an inhibitor for PKA. The PACAP-induced potentiation of NMDA-R was involved in the mRNA expression of Bdnf or c-fos but not Pdyn. These results suggest PACAP to be an upstream regulator for inducing Pdyn mRNA expression through PKA.
authors: Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors: Ying Xu
authors: YX
authors: Dong
authors: Mamoru
authors: M
authors: Fukuchi
authors: Minami
authors: M
authors: Inoue
authors: Ichiro
authors: I
authors: Takasaki
authors: Akiko
authors: A
authors: Tabuchi
authors: Chun Fu
authors: CF
authors: Wu
authors: Masaaki
authors: M
authors: Tsuda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism* / Q000502:physiology; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D004745:Enkephalins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors; D012333:RNA, Messenger; C033660:preproenkephalin