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Diacylglycerol activates the influx of extracellular cations in T-lymphocytes independently of intracellular calcium-store depletion and possibly involving endogenous TRP6 gene products.
- Source :
-
The Biochemical journal [Biochem J] 2002 May 15; Vol. 364 (Pt 1), pp. 245-54. - Publication Year :
- 2002
-
Abstract
- In Jurkat and human peripheral blood T-lymphocytes, 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeant analogue of diacylglycerol, activated the influx of Ca(2+), Ba(2+) and Sr(2+). OAG also caused plasma-membrane depolarization in Ca(2+)-free media that was recovered by the addition of bivalent cation, indicating the activation of Na(+) influx. OAG-induced cation influx was (i) mimicked by the natural dacylglycerol 1-stearoyl-2-arachidonyl-sn-glycerol, (ii) not blocked by inhibiting protein kinase C or in the absence of phospholipase C activity and (iii) blocked by La(3+) and Gd(3+). Differently from OAG, both thapsigargin and phytohaemagglutinin activated a potent influx of Ca(2+), but little influx of Ba(2+) and Sr(2+). Moreover, the influx of Ca(2+) activated by thapsigargin and that activated by OAG were additive. Furthermore, several drugs (i.e. econazole, SKF96365, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, 2-aminoethoxy diphenylborate and calyculin-A), while inhibiting the influx of Ca(2+) induced by both thapsigargin and phytohaemagglutinin, did not affect OAG-stimulated cation influx. Transient receptor potential (TRP) 3 and TRP6 proteins have been shown previously to be activated by diacylglycerol when expressed heterologously in animal cells [Hofmann, Obukhov, Schaefer, Harteneck, Gudermann and Schultz (1999) Nature (London) 397, 259-263]. In both Jurkat and peripheral blood T-lymphocytes, mRNA encoding TRP proteins 1, 3, 4 and 6 was detected by reverse transcriptase PCR, and the TRP6 protein was detected by Western blotting in a purified plasma-membrane fraction. We conclude that T-cells express a diacylglycerol-activated cation channel, unrelated to the channel involved in capacitative Ca(2+) entry, and associated with the expression of TRP6 protein.
- Subjects :
- Barium metabolism
Blotting, Western
Boron Compounds pharmacology
Calcium Channel Blockers pharmacology
Cell Line
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Humans
Imidazoles pharmacology
Jurkat Cells
Membrane Potentials
Phytohemagglutinins metabolism
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Strontium metabolism
TRPC Cation Channels
Thapsigargin pharmacology
Time Factors
Calcium metabolism
Calcium Channels metabolism
Cations
Diglycerides metabolism
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 364
- Issue :
- Pt 1
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 11988098
- Full Text :
- https://doi.org/10.1042/bj3640245