title: Regulation of the Y1 neuropeptide Y receptor gene expression in PC12 cells.
abstract: The Y1 receptor for neuropeptide Y (NPY-Y1) is constitutively expressed in PC12 cells. In this study, we examined the role of nerve growth factor (NGF), pituitary adenylyl cyclase activating polypeptide (PACAP) and dexamethasone on the expression of the gene encoding the rat NPY-Y1 receptor in PC12 cells. A fusion gene (pY1-Luc) was constructed where the reporter enzyme firefly luciferase was placed under the control of 700 bp of the promoter region of the rat NPY-Y1 receptor gene. This promoter region contains recognition consensus sequences for various transcription factors, including one activation protein-1 (AP-1) site, two cyclic AMP responsive element sites, one estrogen receptor element site and four glucocorticoid receptor element sites. NGF increased luciferase activity in a concentration dependent manner. This increase was inhibited by K-252a, a trk A receptor inhibitor, and calphostin C, a PKC inhibitor. PACAP-38 increased luciferase activity in a concentration dependent manner. This activation was inhibited by H-89. Dexamethasone increased transcription of NPY-Y1 gene in PC12 cells. These results indicate that differentiation of PC12 cells into endocrine-like phenotype by dexamethasone and into a neuronal-like phenotype by either NGF or PACAP-38 increases the transcriptional activity of the NPY-Y1 receptor gene in PC12 cells.
authors.affiliation: Division of Biochemistry and Molecular Biology and Department of Medicine and Therapeutics, University of Glasgow, G12 8QQ, Glasgow, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Bournat
authors.forename: J M
authors.initials: JM
authors.lastname: Allen
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D015290:Second Messenger Systems / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
chemical_list: C495403:Adcyap1 protein, rat; D005938:Glucocorticoids; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D003907:Dexamethasone; D020932:Nerve Growth Factor; D008156:Luciferases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C