title: Protein kinase A-dependent substance P expression by pituitary adenylate cyclase-activating polypeptide in rat sensory neuronal cell line ND7/23 cells.
abstract: The neurotrophic effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on rat sensory neuronal cell line ND7/23 cells were investigated. PACAP caused a concentration-dependent increase in the number of neurite-bearing cells and the expression of the substance P precursor (PPT) mRNA in 24 h. The effects of PACAP were mimicked by vasoactive intestinal polypeptide with lower potency and dibutyryl-cyclic AMP, and inhibited by inhibitors of protein kinase A, ERK kinase or p38 kinase, KT5720, U0126, or SB203580, respectively. In a PPT promoter luciferase reporter assay, the increase of PPT mRNA was the result of an increase in PPT gene transcriptional activity by PACAP. The increasing effects of PACAP on PPT mRNA were similarly observed in primary cultured rat dorsal root ganglion cells. Thus, PACAP could induce differentiation-like phenomena in sensory neurons in a cAMP-, protein kinase A-, ERK kinase-, and p38 kinase-dependent manner. These results provide evidence of the neurotrophic action of PACAP, which may function to rescue damaged neurons or to switch the neuronal phenotype in injured or inflamed sensory neurons.
authors.affiliation: Department of Pharmacotherapeutics, Fukuyama University, Sanzo, Gakuencho-1, Fukuyama, Hiroshima 729-0292, Japan. ainoue@fupharm.fukuyama-u.ac.jp
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inoue
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Chiharu
authors.initials: C
authors.lastname: Fukutomi
authors.forename: Miho
authors.initials: M
authors.lastname: Kanoh
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Miyauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
authors.forename: Daiju
authors.initials: D
authors.lastname: Tsuchiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishio
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D010641:Phenotype; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects*; D013373:Substance P / Q000096:biosynthesis* / Q000235:genetics; D015320:Tachykinins / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D047428:Protein Kinase Inhibitors; D011498:Protein Precursors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases