Diacylglycerol activates the influx of extracellular cations in T-lymphocytes independently of intracellular calcium-store depletion and possibly involving endogenous TRP6 gene products

Biochem J. 2002 May 15;364(Pt 1):245-54. doi: 10.1042/bj3640245.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Barium / metabolism
  • Blotting, Western
  • Boron Compounds / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / metabolism*
  • Cations*
  • Cell Line
  • Diglycerides / metabolism*
  • 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
  • T-Lymphocytes / metabolism*
  • TRPC Cation Channels
  • Thapsigargin / pharmacology
  • Time Factors


  • Boron Compounds
  • Calcium Channel Blockers
  • Calcium Channels
  • Cations
  • Diglycerides
  • Enzyme Inhibitors
  • Imidazoles
  • Phytohemagglutinins
  • RNA, Messenger
  • TRPC Cation Channels
  • Barium
  • Thapsigargin
  • 2-aminoethoxydiphenyl borate
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Calcium
  • Strontium