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The Dopamine D3 Receptor Regulates the Effects of Methamphetamine on LPS-induced Cytokine Production in Murine Mast Cells

Li Xue, Xia Li, Hui-Xun Ren, Feng Wu, Ming Li, Biao Wang, Fang-Yuan Chen, Wei-Ying Cheng, Ju-Ping Li, Yan-Jiong Chen, Teng Chen

Immunobiology. 2015 Jun;220(6):744-52.

PMID: 25601390

Abstract:

Previous studies have demonstrated that methamphetamine (METH) alter inflammatory and anti-inflammatory cytokine production in the periphery. However, the effect of METH on lipopolysaccharide (LPS)-induced immune responses and its underlying mechanism of action remains unclear. The dopamine D3 receptor (D3R) plays an important role in METH addiction, indicating that the D3R may regulate METH-mediated immune responses. In this study, we examined the effect of METH on mast cell released cytokines in the lungs and thymi of mice stimulated by LPS, and on LPS-induced murine bone marrow-derived mast cells (BMMCs). Moreover, we used D3R-deficient mice to investigate the effect of this receptor on LPS-stimulated mast cell released cytokine production after METH treatment in the lungs and thymi. The effects of a D3R agonist and antagonist on LPS-induced cytokine production after METH treatment in murine BMMCs were also evaluated. METH suppressed LPS-induced cytokine production in the lungs and thymi of wild-type (WT) mice and BMMCs. However, METH did not alter LPS-induced cytokine production in the lungs and thymi of D3R-deficient mice. When BMMCs were treated with the D3R receptor antagonist, NGB2904 hydrochloride (NGB-2904), METH did not alter LPS-induced cytokine production. However, treatment with the D3R agonist, 7-hydroxy-(di-n-propylamino) tetralin (7-OH-DPAT), significantly enhanced the effects of METH on LPS-induced cytokine production. Our results suggest that METH regulates mast cell released cytokines production in an LPS-induced mouse model via the D3R.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP189061118 NGB 2904 hydrochloride NGB 2904 hydrochloride 189061-11-8 Price
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