title: Methamphetamine induces trace amine-associated receptor 1 (TAAR1) expression in human T lymphocytes: role in immunomodulation.
abstract: The novel transmembrane G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), represents a potential, direct target for drugs of abuse and monoaminergic compounds, including amphetamines. For the first time, our studies have illustrated that there is an induction of TAAR1 mRNA expression in resting T lymphocytes in response to methamphetamine. Methamphetamine treatment for 6 h significantly increased TAAR1 mRNA expression (P < 0.001) and protein expression (P < 0.01) at 24 h. With the use of TAAR1 gene silencing, we demonstrate that methamphetamine-induced cAMP, a classic response to methamphetamine stimulation, is regulated via TAAR1. We also show by TAAR1 knockdown that the down-regulation of IL-2 in T cells by methamphetamine, which we reported earlier, is indeed regulated by TAAR1. Our results also show the presence of TAAR1 in human lymph nodes from HIV-1-infected patients, with or without a history of methamphetamine abuse. TAAR1 expression on lymphocytes was largely in the paracortical lymphoid area of the lymph nodes with enhanced expression in lymph nodes of HIV-1-infected methamphetamine abusers rather than infected-only subjects. In vitro analysis of HIV-1 infection of human PBMCs revealed increased TAAR1 expression in the presence of methamphetamine. In summary, the ability of methamphetamine to activate trace TAAR1 in vitro and to regulate important T cell functions, such as cAMP activation and IL-2 production; the expression of TAAR1 in T lymphocytes in peripheral lymphoid organs, such as lymph nodes; and our in vitro HIV-1 infection model in PBMCs suggests that TAAR1 may play an important role in methamphetamine -mediated immune-modulatory responses.
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Uma
authors: U
authors: Sriram
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Jonathan M
authors: JM
authors: Cenna
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Bijayesh
authors: B
authors: Haldar
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Nicole C
authors: NC
authors: Fernandes
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Roshanak
authors: R
authors: Razmpour
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Shongshan
authors: S
authors: Fan
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Servio H
authors: SH
authors: Ramirez
authors: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA raghava.potula@tuhs.temple.edu.
authors: Raghava
authors: R
authors: Potula
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007376:Interleukin-2 / Q000378:metabolism; D008694:Methamphetamine / Q000009:adverse effects / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D000095383:Trace Amine-Associated Receptors
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007376:Interleukin-2; D008694:Methamphetamine; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors
keywords: HIV infection; T cells; drug abuse; immune response