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Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells.
J Leukoc Biol. 2004 May; 75(5):884-92.JL

Abstract

Cannabinoids exhibit broad immune modulating activity by targeting many cell types within the immune system, including T cells, which exhibit sensitivity, as evidenced by altered activation, proliferation, and cytokine expression. As a result of the critical role calcium plays in T cell function coupled with previous findings demonstrating disruption of the calcium-regulated transcription factor, nuclear factor of activated T cells, by cannabinoid treatment, the objective of the present investigation was to perform an initial characterization of the role of the cannabinoid receptors in the regulation of the intracellular calcium concentration ([Ca(2+)](i)) by delta(9)-tetrahydrocannabinol (delta(9)-THC) in T lymphocytes. Here, we demonstrate that delta(9)-THC robustly elevates [Ca(2+)](i) in purified murine splenic T cells and in the human peripheral blood acute lymphoid leukemia (HPB-ALL) human T cell line but only minimally elevates [Ca(2+)](i) in Jurkat E6-1 (dysfunctional cannabinoid receptor 2-expressing) human T cells. Removal of extracellular calcium severely attenuated the delta(9)-THC-mediated rise in [Ca(2+)](i) in murine splenic T cells and HPB-ALL cells. Pretreatment with cannabinoid receptor antagonists, SR144528 and/or SR141716A, led to an attenuation of delta(9)-THC-mediated elevation in [Ca(2+)](i) in splenic T cells and HPB-ALL cells but not in Jurkat E6-1 cells. Furthermore, pretreatment of HPB-ALL cells with SR144528 antagonized the small rise in [Ca(2+)](i) elicited by delta(9)-THC in the absence of extracellular calcium. These findings suggest that delta(9)-THC induces an influx of extracellular calcium in resting T cells in a cannabinoid receptor-dependent manner.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14966196

Citation

Rao, Gautham K., et al. "Cannabinoid Receptor-mediated Regulation of Intracellular Calcium By Delta(9)-tetrahydrocannabinol in Resting T Cells." Journal of Leukocyte Biology, vol. 75, no. 5, 2004, pp. 884-92.
Rao GK, Zhang W, Kaminski NE. Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells. J Leukoc Biol. 2004;75(5):884-92.
Rao, G. K., Zhang, W., & Kaminski, N. E. (2004). Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells. Journal of Leukocyte Biology, 75(5), 884-92.
Rao GK, Zhang W, Kaminski NE. Cannabinoid Receptor-mediated Regulation of Intracellular Calcium By Delta(9)-tetrahydrocannabinol in Resting T Cells. J Leukoc Biol. 2004;75(5):884-92. PubMed PMID: 14966196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells. AU - Rao,Gautham K, AU - Zhang,Wei, AU - Kaminski,Norbert E, Y1 - 2004/02/13/ PY - 2004/2/18/pubmed PY - 2004/6/21/medline PY - 2004/2/18/entrez SP - 884 EP - 92 JF - Journal of leukocyte biology JO - J Leukoc Biol VL - 75 IS - 5 N2 - Cannabinoids exhibit broad immune modulating activity by targeting many cell types within the immune system, including T cells, which exhibit sensitivity, as evidenced by altered activation, proliferation, and cytokine expression. As a result of the critical role calcium plays in T cell function coupled with previous findings demonstrating disruption of the calcium-regulated transcription factor, nuclear factor of activated T cells, by cannabinoid treatment, the objective of the present investigation was to perform an initial characterization of the role of the cannabinoid receptors in the regulation of the intracellular calcium concentration ([Ca(2+)](i)) by delta(9)-tetrahydrocannabinol (delta(9)-THC) in T lymphocytes. Here, we demonstrate that delta(9)-THC robustly elevates [Ca(2+)](i) in purified murine splenic T cells and in the human peripheral blood acute lymphoid leukemia (HPB-ALL) human T cell line but only minimally elevates [Ca(2+)](i) in Jurkat E6-1 (dysfunctional cannabinoid receptor 2-expressing) human T cells. Removal of extracellular calcium severely attenuated the delta(9)-THC-mediated rise in [Ca(2+)](i) in murine splenic T cells and HPB-ALL cells. Pretreatment with cannabinoid receptor antagonists, SR144528 and/or SR141716A, led to an attenuation of delta(9)-THC-mediated elevation in [Ca(2+)](i) in splenic T cells and HPB-ALL cells but not in Jurkat E6-1 cells. Furthermore, pretreatment of HPB-ALL cells with SR144528 antagonized the small rise in [Ca(2+)](i) elicited by delta(9)-THC in the absence of extracellular calcium. These findings suggest that delta(9)-THC induces an influx of extracellular calcium in resting T cells in a cannabinoid receptor-dependent manner. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/14966196/Cannabinoid_receptor_mediated_regulation_of_intracellular_calcium_by_delta_9__tetrahydrocannabinol_in_resting_T_cells_ L2 - https://doi.org/10.1189/jlb.1203638 DB - PRIME DP - Unbound Medicine ER -