δ-Opioid receptors stimulate ERK1/2 activity in NG108-15 hybrid cells by integrin-mediated transactivation of TrkA receptors

Edited by Lukas Huber

Received 30 May 2008; received in revised form 11 August 2008; accepted 23 August 2008. published online 05 September 2008.

Abstract

This study demonstrates that activation of δ-opioid receptors (DORs) in neuroblastoma×glioma (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.

Abbreviations: DADLE, [d-Ala2, d-Leu5]enkephalin, DOR, δ-opioid receptor, EGF, epidermal growth factor, ERK, extracellular signal-regulated protein kinase, FN, fibronectin, NG108-15 cells, neuroblastoma

glioma (NG108-15) hybrid cells, TrkA, tropomyosin-related kinase A

Keywords: Cell adhesion, δ-Opioid receptor, Integrin, Extracellular signal-regulated protein kinase, Tropomyosin-related kinase A

Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Koeniginstrasse 16, 80539 Muenchen, Germany

Corresponding author. Fax: +49 89 2180 16556.

PII: S0014-5793(08)00708-4

doi:10.1016/j.febslet.2008.08.021

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