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- Title
A role for 5,6-epoxyeicosatrienoic acid in calcium entry by de novo conformational coupling in human platelets.
- Authors
Ben-Amor, Nidhal; Redondo, Pedro C.; Bartegi, Aghleb; Pariente, José A.; Salido, Ginés M.; Rosado, Juan A.
- Abstract
A major pathway for Ca2+ entry in non-excitable cells is activated following depletion of intracellular Ca2+ stores. A de novo conformational coupling between elements in the plasma membrane (PM) and Ca2+ stores has been proposed as the most likely mechanism to activate this capacitative Ca2+ entry (CCE) in several cell types, including platelets. Here we report that a cytochrome P450 metabolite, 5,6-EET, might be a component of the de novo conformational coupling in human platelets. In these cells, 5,6-EET induces divalent cation entry without having any detectable effect on Ca2+ store depletion. 5,6-EET-induced Ca2+ entry was sensitive to the CCE blockers 2-APB, lanthanum, SKF-96365 and nickel and impaired by incubation with anti-hTRPC1 antibody. Ca2+ entry stimulated by low concentrations of thapsigargin, which selectively depletes the dense tubular system and induces EET production, was impaired by the cytochrome P450 inhibitor 17-ODYA, which has no effect on CCE mediated by depletion of the acidic stores using 2,5-di-(tert-butyl)-1,4-hydroquinone. We have found that 5,6-EET-induced Ca2+ entry requires basal levels of H2O2, which might maintain a redox state favourable for this event. Finally, our results indicate that 5,6-EET induces the activation of tyrosine kinase proteins and the reorganization of the actin cytoskeleton, which might provide a support for the transport of portions of the Ca2+ store towards the PM to facilitate de novo coupling between IP3R type II and hTRPC1 detected by coimmunoprecipitation. We propose that the involvement of 5,6-EET in TG-induced coupling between IP3R type II and hTRPC1 and subsequently CCE is compatible with the de novo conformational coupling in human platelets.
- Subjects
CELL membranes; BLOOD platelets; CYTOCHROME P-450; CELLS; METABOLITES
- Publication
Journal of Physiology, 2006, Vol 570, Issue 2, p309
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2005.100800