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Induction of intracellular calcium elevation by Delta9-tetrahydrocannabinol in T cells involves TRPC1 channels.
J Leukoc Biol. 2006 Jan; 79(1):202-13.JL

Abstract

We have reported previously that Delta9-tetrahydrocannabinol (Delta9-THC) treatment of resting human and murine splenic T cells robustly elevated intracellular calcium ([Ca2+]i). The objective of the present investigation was to examine the putative role of [Ca2+]i store depletion and store-operated calcium (SOC) and receptor-operated cation (ROC) channels in the mechanism by which Delta9-THC increases [Ca2+]i in the cannabinoid-2 receptor-expressing human peripheral blood-acute lymphoid leukemia (HPB-ALL) human T cell line. By using the smooth endoplasmic reticulum Ca2+-ATPase pump inhibitor, thapsigargin, and the ryanodine receptor antagonist, 8-bromo-cyclic adenosine diphosphate ribose, we demonstrate that the Delta9-THC-mediated elevation in [Ca2+]i occurs independently of [Ca2+]i store depletion. Furthermore, the ROC channel inhibitor, SK&F 96365 was more efficacious at attenuating the Delta9-THC-mediated elevation in [Ca2+]i than SOC channel inhibitors, 2-aminoethoxydiphenyl borate and La3+. Recently, several members of the transient receptor potential canonical (TRPC) channel subfamily have been suggested to operate as SOC or ROC channels. In the present studies, treatment of HPB-ALL cells with 1-oleoyl-2-acetyl-sn-glycerol (OAG), a cell-permeant analog of diacylglycerol (DAG), which gates several members of the TRPC channel subfamily, rapidly elevated [Ca2+]i, as well as prevented a subsequent, additive elevation in [Ca2+]i by Delta9-THC, independent of protein kinase C. Reverse transcriptase-polymerase chain reaction analysis for TRPC1-7 showed that HPB-ALL cells express detectable mRNA levels of only TRPC1. Finally, small interference RNA knockdown of TRPC1 attenuated the Delta9-THC-mediated elevation of [Ca2+]i. Collectively, these results suggest that Delta9-THC-induced elevation in [Ca2+]i is attributable entirely to extracellular calcium influx, which is independent of [Ca2+]i store depletion, and is mediated, at least partially, through the DAG-sensitive TRPC1 channels.

Authors+Show Affiliations

Department of Pharmacology & Toxicology, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16244107

Citation

Rao, Gautham K., and Norbert E. Kaminski. "Induction of Intracellular Calcium Elevation By Delta9-tetrahydrocannabinol in T Cells Involves TRPC1 Channels." Journal of Leukocyte Biology, vol. 79, no. 1, 2006, pp. 202-13.
Rao GK, Kaminski NE. Induction of intracellular calcium elevation by Delta9-tetrahydrocannabinol in T cells involves TRPC1 channels. J Leukoc Biol. 2006;79(1):202-13.
Rao, G. K., & Kaminski, N. E. (2006). Induction of intracellular calcium elevation by Delta9-tetrahydrocannabinol in T cells involves TRPC1 channels. Journal of Leukocyte Biology, 79(1), 202-13.
Rao GK, Kaminski NE. Induction of Intracellular Calcium Elevation By Delta9-tetrahydrocannabinol in T Cells Involves TRPC1 Channels. J Leukoc Biol. 2006;79(1):202-13. PubMed PMID: 16244107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of intracellular calcium elevation by Delta9-tetrahydrocannabinol in T cells involves TRPC1 channels. AU - Rao,Gautham K, AU - Kaminski,Norbert E, Y1 - 2005/10/21/ PY - 2005/10/26/pubmed PY - 2006/3/3/medline PY - 2005/10/26/entrez SP - 202 EP - 13 JF - Journal of leukocyte biology JO - J Leukoc Biol VL - 79 IS - 1 N2 - We have reported previously that Delta9-tetrahydrocannabinol (Delta9-THC) treatment of resting human and murine splenic T cells robustly elevated intracellular calcium ([Ca2+]i). The objective of the present investigation was to examine the putative role of [Ca2+]i store depletion and store-operated calcium (SOC) and receptor-operated cation (ROC) channels in the mechanism by which Delta9-THC increases [Ca2+]i in the cannabinoid-2 receptor-expressing human peripheral blood-acute lymphoid leukemia (HPB-ALL) human T cell line. By using the smooth endoplasmic reticulum Ca2+-ATPase pump inhibitor, thapsigargin, and the ryanodine receptor antagonist, 8-bromo-cyclic adenosine diphosphate ribose, we demonstrate that the Delta9-THC-mediated elevation in [Ca2+]i occurs independently of [Ca2+]i store depletion. Furthermore, the ROC channel inhibitor, SK&F 96365 was more efficacious at attenuating the Delta9-THC-mediated elevation in [Ca2+]i than SOC channel inhibitors, 2-aminoethoxydiphenyl borate and La3+. Recently, several members of the transient receptor potential canonical (TRPC) channel subfamily have been suggested to operate as SOC or ROC channels. In the present studies, treatment of HPB-ALL cells with 1-oleoyl-2-acetyl-sn-glycerol (OAG), a cell-permeant analog of diacylglycerol (DAG), which gates several members of the TRPC channel subfamily, rapidly elevated [Ca2+]i, as well as prevented a subsequent, additive elevation in [Ca2+]i by Delta9-THC, independent of protein kinase C. Reverse transcriptase-polymerase chain reaction analysis for TRPC1-7 showed that HPB-ALL cells express detectable mRNA levels of only TRPC1. Finally, small interference RNA knockdown of TRPC1 attenuated the Delta9-THC-mediated elevation of [Ca2+]i. Collectively, these results suggest that Delta9-THC-induced elevation in [Ca2+]i is attributable entirely to extracellular calcium influx, which is independent of [Ca2+]i store depletion, and is mediated, at least partially, through the DAG-sensitive TRPC1 channels. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/16244107/Induction_of_intracellular_calcium_elevation_by_Delta9_tetrahydrocannabinol_in_T_cells_involves_TRPC1_channels_ L2 - https://doi.org/10.1189/jlb.0505274 DB - PRIME DP - Unbound Medicine ER -