Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells. 1496 96

This laboratory has reported previously that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabinol (CBN) robustly elevate intracellular calcium ([Ca(2+)](i)) in resting human and murine T cells, whereas CP55,940 [5-(1,1-dimethylheptyl)-2-(5-hydroxy-2-(3-hydroxypropyl)cyclohexyl)phenol], a high-affinity ligand for CB1 and CB2, does not. In light of our previous studies, the objective of the present investigation was to examine the ability of various cannabinoid compounds to elevate [Ca(2+)](i) in the CB2 receptor-expressing human peripheral blood acute lymphoid leukemia T cell line and the dependence of structural similarity to Delta(9)-THC therein. The present studies demonstrate that CBN and HU-210 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol], both tricyclic and in that respect structurally similar to Delta(9)-THC, elevate [Ca(2+)](i). The [Ca(2+)](i) elevation elicited by both CBN and HU-210 was attenuated upon removal of extracellular calcium and upon pretreatment with SK&F96365 [1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole], an inhibitor of receptor-operated cation channels. In addition, pretreatment with either CB1 or CB2 receptor antagonists attenuated the CBN- and HU-210-mediated [Ca(2+)](i) elevation. Further investigation of the dependence of Delta(9)-THC, CBN, and HU-210 on cannabinoid receptors using splenocytes from wild-type and CB1(-/-)/CB2(-/-) mice showed that the [Ca(2+)](i) elevation elicited by all three tricyclic cannabinoids was independent of CB1 and CB2. Moreover, both the CB1 and CB2 receptor antagonists attenuated that rise in [Ca(2+)](i) elicited by the tricyclic cannabinoids in the wild-type and CB1(-/-)/CB2(-/-) mouse splenocytes. Taken together, the present results demonstrate that classic tricyclic cannabinoids with structural similarity to Delta(9)-THC elicit a robust influx of calcium in T cells putatively through receptor-operated cation channels in a manner sensitive to the cannabinoid receptor antagonists, but independent of the CB1 and CB2 receptors.
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PMID:Cannabinoid-mediated elevation of intracellular calcium: a structure-activity relationship. 1643 96