Inositol 1,4,5-trisphosphate-independent calcium signalling by platelet-derived growth factor in the human SH-SY5Y neuroblastoma cell

Abstract

In adherent SH-SY5Y human neuroblastoma cells, activation of G-protein-coupled muscarinic M3receptors evoked a biphasic elevation of both intracellular [Ca2+] ([Ca2+]i) and inositol-1,4,5-trisphosphate (D-Ins(1,4,5)P3) mass. In both cases, temporal profiles consisted of rapid transient elevations followed by a decline to a lower, yet sustained level. In contrast, platelet-derived growth factor (PDGF), a receptor tyrosine kinase agonist acting via PDGF receptor b chains in these cells, elicited a slow and transient elevation of [Ca2+]ithat returned to basal levels within5 to 10min with no evidence of inositol phosphate generation. Full responses for either receptor type required intracellular and extracellular Ca2+and mobilization of a shared thapsigargin-sensitive intracellular Ca2+store. Strategiesthat affected the ability of D-Ins(1,4,5)P3to interact with the Ins(1,4,5)P3-receptor demonstrated an Ins(1,4,5)P3-dependency of the muscarinic receptor-mediated elevation of [Ca2+]ibut showed that PDGF-mediated elevations of [Ca2+]iare Ins(1,4,5)P3-independent in these cells.