Pituitary adenylate cyclase-activating polypeptide (PACAP) is an upstream regulator of prodynorphin mRNA expression in neurons.
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.
Dong
Ying Xu
YX
Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Fukuchi
Mamoru
M
Inoue
Minami
M
Takasaki
Ichiro
I
Tabuchi
Akiko
A
Wu
Chun Fu
CF
Tsuda
Masaaki
M
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*
D004745:Enkephalins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors; D012333:RNA, Messenger; C033660:preproenkephalin