delta-Opioid receptors stimulate ERK1/2 activity in NG108-15 hybrid cells by integrin-mediated transactivation of TrkA receptors.
This study demonstrates that activation of delta-opioid receptors (DORs) in neuroblastomaxglioma (NG108-15) hybrid cells by [D-Ala2, D-Leu5]enkephalin (DADLE) and etorphine significantly enhances cell adhesion to fibronectin-coated wells. This effect is blocked by both naloxone and integrin binding RGDT peptides. In addition, cell adhesion turned out to be a prerequisite for DOR-stimulated transactivation of Tropomyosin-related kinase A (TrkA) and extracellular signal-regulated kinases 1/2 (ERK1/2). Because inhibition of TrkA activation by AG879 completely blocked DOR- and integrin-mediated ERK1/2 signaling, the present results indicate that in NG108-15 cells DOR-stimulated ERK1/2 activation is mediated by integrin-induced transactivation of TrkA.
Eisinger
Daniela A
DA
Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Koeniginstrasse 16, 80539 Muenchen, Germany. Eisinger@lrz.uni-muenchen.de
Ammer
Hermann
H
D002448:Cell Adhesion; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D005910:Glioma; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects / Q000201:enzymology; D016023:Integrins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020917:Receptor, trkA / Q000819:agonists* / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists*; D015533:Transcriptional Activation; D020032:Tyrphostins / Q000494:pharmacology
C081020:AG-879; D016023:Integrins; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D017465:Receptors, Opioid, delta; D020032:Tyrphostins; D009270:Naloxone; D005048:Etorphine; D016308:Enkephalin, Leucine-2-Alanine; D020917:Receptor, trkA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3