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https://www.readbyqxmd.com/read/23639801/a-selective-antagonist-reveals-a-potential-role-of-g-protein-coupled-receptor-55-in-platelet-and-endothelial-cell-function
#1
Julia Kargl, Andrew J Brown, Liisa Andersen, Georg Dorn, Rudolf Schicho, Maria Waldhoer, Akos Heinemann
The G protein-coupled receptor 55 (GPR55) is a lysophosphatidylinositol (LPI) receptor that is also responsive to certain cannabinoids. Although GPR55 has been implicated in several (patho)physiologic functions, its role remains enigmatic owing mainly to the lack of selective GPR55 antagonists. Here we show that the compound CID16020046 ((4-[4-(3-hydroxyphenyl)-3-(4-methylphenyl)-6-oxo-1H,4H,5H,6H-pyrrolo[3,4-c]pyrazol-5-yl] benzoic acid) is a selective GPR55 antagonist. In yeast cells expressing human GPR55, CID16020046 antagonized agonist-induced receptor activation...
July 2013: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/23494519/inhibitory-effects-of-sigma-2-receptor-agonists-on-t-lymphocyte-activation
#2
Miguel A Iñiguez, Carmen Punzón, Raquel Nieto, Javier Burgueño, José M Vela, Manuel Fresno
Sigma (σ) receptor ligands are essentially known for their effects on the nervous system although recent studies have shown their potential effects modulating some other pathophysiological processes as cell proliferation, cancer, and the immune response. Here, we have analyzed the actions of σ-1 and σ-2 receptors ligands on T cell activation. Our results show that treatment of Jurkat T cells with σ-2 agonists decreased the induction of the expression of Interleukin (IL)-2, Tumor necrosis factor (TNF)-α, and Cyclooxygenase (COX)-2 by activated T cells in a dose-dependent manner...
2013: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/18757503/the-gpr55-ligand-l-alpha-lysophosphatidylinositol-promotes-rhoa-dependent-ca2-signaling-and-nfat-activation
#3
Christopher M Henstridge, Nariman A B Balenga, Lesley A Ford, Ruth A Ross, Maria Waldhoer, Andrew J Irving
The endogenous phospholipid l-alpha-lysophosphatidylinositol (LPI) was recently identified as a novel ligand for the orphan G protein-coupled receptor 55 (GPR55). In this study we define the downstream signaling pathways activated by LPI in a human embryonic kidney (HEK) 293 cell line engineered to stably express recombinant human GPR55. We find that treatment with LPI induces marked GPR55 internalization and stimulates a sustained, oscillatory Ca(2+) release pathway, which is dependent on Galpha13 and requires RhoA activation...
January 2009: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/17196940/the-acetaminophen-derived-bioactive-n-acylphenolamine-am404-inhibits-nfat-by-targeting-nuclear-regulatory-events
#4
Francisco J Caballero, Carmen M Navarrete, Sandra Hess, Bernd L Fiebich, Giovanni Appendino, Antonio Macho, Eduardo Muñoz, Rocío Sancho
AM404 is a synthetic TRPV1/CB(1) hybrid ligand with inhibitory activity on the anandamide transporter and is used for the pharmacological manipulation of the endocannabinoid system. It has been recently described that acetaminophen is metabolised in the brain to form the bioactive N-acylphenolamine AM404 and therefore, we have evaluated the effect of this metabolite in human T cells, discovering that AM404 is a potent inhibitor of TCR-mediated T-cell activation. Moreover, we found that AM404 specifically inhibited both IL-2 and TNF-alpha gene transcription and TNF-alpha synthesis in CD3/CD28-stimulated Jurkat T cells in a FAAH independent way...
April 1, 2007: Biochemical Pharmacology
https://www.readbyqxmd.com/read/15774549/2-arachidonoyl-glycerol-suppresses-interferon-gamma-production-in-phorbol-ester-ionomycin-activated-mouse-splenocytes-independent-of-cb1-or-cb2
#5
Barbara L F Kaplan, Yanli Ouyang, Cheryl E Rockwell, Gautham K Rao, Norbert E Kaminski
2-Arachidonoyl-glycerol (2-AG), an endogenous ligand for cannabinoid receptor types 1 and 2 (CB1 and CB2), has previously been demonstrated to modulate immune functions including suppression of interleukin-2 expression and nuclear factor of activated T cells (NFAT) activity. The objective of the present studies was to investigate the effect of 2-AG on interferon-gamma (IFN-gamma) expression and associated upstream signaling events. Pretreatment of splenocytes with 2-AG markedly suppressed phorbol 12-myristate 13-acetate plus calcium ionophore (PMA/Io)-induced IFN-gamma secretion...
June 2005: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/14657699/equivalent-functional-nuclear-factor-of-activated-t-cell-1-mrna-and-protein-expression-in-cord-blood-and-adult-t-cells
#6
Rose Marie O'Neill, Denis J Reen
Cord blood (CB) cells are now an important source of stem cells for bone marrow reconstitution as a result of the decreased risk of graft-versus-host disease that was attributed to previously reported absent or diminished nuclear factor of activated T (NFAT) cell 1 expression by CB T cells. This study reexamines NFAT1 expression in CB T cells. CB T cells were examined for NFAT1 mRNA and protein expression. These cells were then stimulated, and NFAT1 translocation and interleukin-2 production were assessed. Our results show that resting CB CD4+ T cells express NFAT1 mRNA and protein at levels similar to their adult counterparts...
November 27, 2003: Transplantation
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