Mechanisms of integrin-mediated calcium signaling in MDCK cells: regulation of adhesion by IP3- and store-independent calcium influx

摘要: Peptides containing Arg-Gly-Asp (RGD) immobilized on beads bind to integrins and trigger biphasic, transient increases in intracellular free Ca2+ ([Ca2+]i) Madin-Darby canine kidney epithelial cells. The [Ca2+]i increase participates feedback regulation of integrin-mediated adhesion these We examined influx pathways inositol 1,4,5-trisphosphate (IP3)-mediated store release as possible sources the rise. RGD-induced response requires external (threshold approximately 150 microM), its magnitude is proportional extracellular calcium. transients were attenuated by channel inhibitors (Ni2+ carboxy-amidotriazole) or plasma membrane depolarization, indicating that contributes response. Loading cells with heparin reduced size transients, IP3-mediated from stores may also contribute RGD Depletion thapsigargin activated Ni(2+)-sensitive might be expected occur after depletion stored Ca2-. However, elicited a even pretreatment thapsigargin, controlled mechanism independent depletion. conclude result primarily combination two distinct mechanisms: 1) stores, 2) activation pathway regulated independently IP3 release. Because Ni2+ carboxy-amidotriazole inhibited adhesion, whereas had little effect, we suggest most important for increased [Ca2+]i.