title: Epinephrine increases phosphorylation of MAP-2c in rat pheochromocytoma cells (PC12 Cells) via a protein kinase C- and mitogen activated protein kinase-dependent mechanism.
abstract: Adrenoceptors mediate effects of endogenous catecholamines and have been shown to affect the neuronal development. Microtubule-associated protein-2 (MAP-2) is an important cytoskeleton protein whose phosphorylation in response to extracellular signal is involved in the regulation of neurite outgrowth and neuronal plasticity. The present study was designed to determine the effect of activation of adrenoceptor by epinephrine on MAP-2 phosphorylation in differentiation PC12 cells and, if so, to explore the mediating mechanism. We found that epinephrine could significantly increase the phosphorylation of MAP-2c at ser136 in a dose- and time-dependent manner in differentiated PC12 cells as well as microtubule arrays. Differentiated PC12 cells express alpha 2A-adrenoceptor, whose antagonists could block these mentioned effects of epinephrine, and clonidine which is the agonist of alpha 2-adrenoceptor could mimic the effect of epinephrine. Moreover phosphorylation of ERK and PKC was induced by epinephrine, and ERK and PKC specific inhibitors concentration-dependently prevented epinephrine-induced phosphorylation of MAP-2c at ser136. In addition, pretreatment of PC12 cells with epinephrine partly inhibited 30 microM nocodazole induced neurites retraction. These findings suggest that epinephrine induces phosphorylation of MAP-2c at ser136 through a alpha 2-adrenoceptor mediated, ERK/PKC-dependent signaling pathway, which may contribute to the stabilization of neurites.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Tie
authors.forename: Jian-Zhao
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Lin
authors.forename: Tian-Hao
authors.initials: TH
authors.lastname: Su
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Li
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Wu
authors.forename: You-Yi
authors.initials: YY
authors.lastname: Zhang
authors.forename: He-Ming
authors.initials: HM
authors.lastname: Yu
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015151:Immunoblotting; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D053119:Benzophenanthridines; D005419:Flavonoids; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D047428:Protein Kinase Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D012694:Serine; C016299:chelerythrine; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D003000:Clonidine; D015739:Nocodazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004837:Epinephrine