Immune responses in mice to arecoline mediated by lymphocyte muscarinic acetylcholine receptor

Authors

  • Xiao-ming Wen,

    1. Department of Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100094, P.R. China
    2. Department of Cardiovascular Pharmacology, Institute of Pharmacology and Toxicology, 27 Tai Ping Road, Beijing 100850, P.R. China
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  • Ying-li Zhang,

    1. Department of Cardiovascular Pharmacology, Institute of Pharmacology and Toxicology, 27 Tai Ping Road, Beijing 100850, P.R. China
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  • Xin-min Liu,

    1. Department of Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100094, P.R. China
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  • Shun-xing Guo,

    1. Department of Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100094, P.R. China
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  • Hai Wang

    Corresponding author
    1. Department of Cardiovascular Pharmacology, Institute of Pharmacology and Toxicology, 27 Tai Ping Road, Beijing 100850, P.R. China
      Corresponding author. Tel.: +86 10 6693 2651; fax: +86 10 6818 8180. wh9588@yahoo.com.cn
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Corresponding author. Tel.: +86 10 6693 2651; fax: +86 10 6818 8180. wh9588@yahoo.com.cn

Abstract

There is evidence that lymphocytes possess all the components of the cholinergic system independent of neuronal innervations. Thus, potential therapeutic applications of drugs targeting the neuronal cholinergic system might have side effects on the immune system. This study investigated whether arecoline could affect immunological functions in mice and explored the mechanism of the effect of arecoline on the immune system. To investigate this, arecoline at the dose of 2 mg/kg was administered subcutaneously in BALB/c mice for 4 weeks to evaluate changes in immunological function both in vivo and in vitro. Several indices were used to assess immunological activation, including the spleen index, serum hemolysin levels, interleukin (IL)-2 and splenocyte proliferation. Our results showed a significant reduction in treated animals with respect to the control group in the following tests: the spleen index (86%), hemolysin against sheep red blood cells (68%), IL-2 production (73%), and splenocyte proliferation induced by concanavalin A or lipopolysaccharide (76% and 74%, respectively). The muscarinic receptor antagonist atropine (1 mg/kg) reversed the inhibition of the four immune-related parameters mentioned above. Chronic atropine alone did not significantly affect the immune response. To our knowledge, this is the first study to demonstrate that arecoline interferes with the immune system by targeting the muscarinic acetylcholine receptors of the non-neuronal cholinergic system.

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