Journal article
Regulation of mast cell activation by TRP protein-mediated Ca2+ entry

Publication Details
Almering, J.; Tsvilovskyy, V.; Mannebach, S.; Kriebs, U.; Weissgerber, P.; Flockerzi, V.; Birnbaumer, L.; Freichel, M.
Deutsche Gesellschaft für Pharmakologie und Toxikologie
Publication year:
Naunyn-Schmiedeberg's Archives of Pharmacology
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Book title:
Abstracts of the 78th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology. March 19-22, 2012. Dresden, Germany.
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Ca 2+ influx is essential for mast cell activation induced by various ligands. It does not only rely on the opening of Ca 2+ -conducting channels but depends critically on the membrane potential. TRP channels form cation entry channels thereby either contributing to Ca 2+ entry or depolarisation. Recently, we showed that TRPM4 acts as a Ca 2+ -activated non-selective cation channel and critically determines the driving force for Ca 2+ influx in mast cells following Fc ε RI-stimulation. In addition to TRPM4 we also identified the expression of other TRP transcripts in bone marrow derived mast cells (BMMC) including those encoding TRPC2, TRPC3, TRPC5, TRPC6 and TRPM7. In peritoneal mast cells (PMC), RT-PCR indicated expression of TRPC1, TRPC4, TRPC5, TRPC6, TRPM2, TRPM4 and TRPM5. To identify the functional role of those TRP channel proteins for mast cell activation we analysed Ca 2+ signaling using microfluorimetry in BMMCs and PMCs after stimulation with substances known to activate TRPC6 channels in other cell systems such as the diacylglycerol analogue OAG, the hyperforin analogue HYP-9 and flufenamic acid (FFA), but could not evoke a rise in the [Ca 2+ ] i in both PMC and BMMC. Sphingosine 1- phosphate and lysophosphatidylcholine, which were reported to activate TRPC5 channels, induced only minor rise in [Ca 2+ ] i in BMMCs, respectively. Here, we will present our analysis of Ca 2+ signaling following stimulation of the Fc ε RI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels.


Last updated on 2021-04-08 at 14:25