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Endothelins Regulate Arachidonic Acid Release and Mitogen‐Activated Protein Kinase Activity in Schwann Cells
Author(s) -
BertiMattera Lilia.,
Wilkins Pamela L.,
Harwalkar Subash,
Madhun Zuhayr,
Almhanna Khaldoun,
Mattera Rafael
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0752316.x
Subject(s) - mapk/erk pathway , kinase , protein kinase a , microbiology and biotechnology , adenylyl cyclase , mitogen activated protein kinase , stimulation , phospholipase c , p38 mitogen activated protein kinases , chemistry , forskolin , biology , signal transduction , endocrinology , medicine
Immortalized rat Schwann cells (iSC) express endothelin(ET) receptors coupled to inhibition of adenylyl cyclase and stimulation ofphospholipase C (PLC). These effects precede phenotypic changes and increasedDNA synthesis. We have investigated the role of ETs in the regulation ofarachidonic acid (AA) release and mitogen‐activated protein kinases (MAPKs).Both ET‐1 and ET‐3 increased AA release in iSC. This effect was sensitive tothe phospholipase A 2 (PLA 2 ) inhibitors E ‐6‐(bromomethylene)tetrahydro‐3‐(1‐naphthalenyl)‐2 H ‐pyran‐2‐oneand arachidonyl‐trifluoromethyl ketone but was insensitive to inhibitors ofPLC or phospholipase D‐dependent diacylglycerol generation. ET‐1‐dependent AArelease was also unaffected by removal of extracellular Ca 2+ andblocking the concomitant elevation in [Ca 2+ ] i ,consistent with participation of a Ca 2+ ‐independentPLA 2 . Treatment of iSC with ETs also resulted in activation ofextracellular signal‐regulated kinase, c‐Jun‐NH 2 ‐terminal kinase(JNK), and p38 MAPK. A cause‐effect relationship between agonist‐dependent AArelease and stimulation of MAPKs, but not the opposite, was suggested byactivation of JNK by exogenous AA and by the observation that inhibition ofMAPK kinase or p38 MAPK was inconsequential to ET‐1‐induced AA release.Similar effects of ETs on AA release and MAPK activity were observed incultures expanded from primary SC and in iSC. Regulation of these effectorsmay mediate the control of proliferation and differentiation of SC by ETsduring peripheral nerve development and regeneration.