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

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