title: Mechanism of isoproterenol-induced RGS2 up-regulation in astrocytes.
abstract: Regulators of G protein signaling (RGSs) are inducibly expressed in response to various stimuli and the up-regulation of RGSs leads to significant decreases in GPCR responsiveness. Isoproterenol, an adrenergic receptor agonist, stimulated RGS2 mRNA in C6 rat astrocytoma cells. The up-regulation of RGS2 mRNA was abrogated by genistein, a protein tyrosine kinase inhibitor (PTK), and by broad-spectrum protein kinase C (PKC) inhibitors (staurosporine and GF109203X). alpha-Adrenergic antagonist (prazocin), beta-adrenergic antagonist (prazocin), and pertussis toxin only partially blocked the RGS2 up-regulation, suggesting that the RGS2 up-regulation is concomitantly mediated by Galphai, Galphas, and Galphaq. It is interesting to note that SB203580, a potent p38 mitogen-activated protein kinase (MAPK) inhibitor, completely inhibited the isoproterenol-mediated RGS2 expression. In addition, isoproterenol also markedly stimulated RGS2 mRNA in rat primary astrocytes, which were sensitive to SB203580 and staurosporine. Therefore, our data suggest that adrenergic receptor-mediated signaling (induced by isoproterenol) may be involved in the regulation of RGS2 expression in astrocytes via activating PTK, PKC, and p38 MAPK.
authors.affiliation: Laboratory of Physiology and Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Sung Dae
authors.initials: SD
authors.lastname: Kim
authors.forename: Whi Min
authors.initials: WM
authors.lastname: Lee
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.forename: Seung Chun
authors.initials: SC
authors.lastname: Park
authors.forename: Sang Keun
authors.initials: SK
authors.lastname: Kim
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D019833:Genistein / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D020710:RGS Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology; D051381:Rats; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D020710:RGS Proteins; C514563:RGS2 protein, rat; D019833:Genistein; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D007545:Isoproterenol