1. Protein Kinase A-Dependent Substance P Expression by Pituitary Adenylate Cyclase-Activating Polypeptide in Rat Sensory Neuronal Cell Line ND7/23 Cells
- Author
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Mutsumi Miyauchi, Masatoshi Ohnishi, Atsuko Inoue, Takashi Takata, Chiharu Fukutomi, Hiroaki Nishio, Daiju Tsuchiya, and Miho Kanoh
- Subjects
Male ,endocrine system ,Sensory Receptor Cells ,Transcription, Genetic ,Recombinant Fusion Proteins ,p38 mitogen-activated protein kinases ,Adenylate kinase ,Hybrid Cells ,Substance P ,p38 Mitogen-Activated Protein Kinases ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Dorsal root ganglion ,Genes, Reporter ,Ganglia, Spinal ,Tachykinins ,Neurites ,medicine ,Animals ,heterocyclic compounds ,RNA, Messenger ,Protein Precursors ,Rats, Wistar ,Extracellular Signal-Regulated MAP Kinases ,Protein kinase A ,Protein Kinase Inhibitors ,Cells, Cultured ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Differentiation ,General Medicine ,KT5720 ,Cyclic AMP-Dependent Protein Kinases ,Molecular biology ,Sensory neuron ,Rats ,Phenotype ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,Cell culture ,biology.protein ,Pituitary Adenylate Cyclase-Activating Polypeptide ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,Neurotrophin - 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.
- Published
- 2012
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