Mechanism of isoproterenol-induced RGS2 up-regulation in astrocytes.
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.
Kim
Sung Dae
SD
Laboratory of Physiology and Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Lee
Whi Min
WM
Suk
Kyoungho
K
Park
Seung Chun
SC
Kim
Sang Keun
SK
Cho
Jae Youl
JY
Rhee
Man Hee
MH
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
D004791:Enzyme Inhibitors; D020710:RGS Proteins; C514563:RGS2 protein, rat; D019833:Genistein; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D007545:Isoproterenol