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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Chronic Self-Administration of Nicotine in Rats Impairs T Cell Responsiveness

Roma Kalra, Shashi P. Singh, Dean Kracko, Shannon G. Matta, Burt M. Sharp and Mohan L. Sopori
Journal of Pharmacology and Experimental Therapeutics September 2002, 302 (3) 935-939; DOI: https://doi.org/10.1124/jpet.302.3.935
Roma Kalra
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Shashi P. Singh
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Dean Kracko
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Shannon G. Matta
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Burt M. Sharp
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Mohan L. Sopori
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Abstract

Chronic exposure of rodents to nicotine via subcutaneously or intracerebroventricularly implanted miniosmotic pumps affects T cell function. However, this method of continuous nicotine administration does not replicate the self-motivated administration of nicotine in human smokers. To determine whether nicotine impairs the immune system under conditions pertinent to human smokers, we investigated the T cell responsiveness of male Lewis rats self-administering (SA) nicotine (0.03 mg/kg of body weight per injection) 40 to 50 times/day for 5 weeks, using a model of virtually unlimited access to nicotine. Compared with sham control animals, the concanavalin A-induced proliferation of spleen cells from SA rats was significantly decreased. Moreover, the ability of spleen cells to mobilize intracellular Ca2+ after ligation of the T cell antigen receptor (TCR) with an anti-αβ TCR antibody was significantly less in SA than in control rats. In addition, inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular Ca2+ stores were markedly depleted in spleen cells from SA animals. These results suggest that chronic nicotine self-administration suppresses T cell responsiveness, and this suppression may result from an impaired TCR-mediated signaling that stems from the depletion of IP3-sensitive intracellular Ca2+ stores.

Footnotes

  • This study was funded in part by National Institutes of Health Grants DA-04208 (to M.L.S.), DA-03977 (to B.M.S.), and DA-04196 (to B.M.S.).

  • Abbreviations:
    TCR
    T cell antigen receptor
    [Ca2+]i
    intracellular ionized calcium concentration
    IP3
    inositol 1,4,5-trisphosphate
    SA
    self-administering
    PBS
    phosphate-buffered saline
    Con A
    concanavalin A
    Ab
    antibody
    mAb
    monoclonal Ab
    • Received October 17, 2001.
    • Accepted March 8, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 302 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 302, Issue 3
1 Sep 2002
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Chronic Self-Administration of Nicotine in Rats Impairs T Cell Responsiveness

Roma Kalra, Shashi P. Singh, Dean Kracko, Shannon G. Matta, Burt M. Sharp and Mohan L. Sopori
Journal of Pharmacology and Experimental Therapeutics September 1, 2002, 302 (3) 935-939; DOI: https://doi.org/10.1124/jpet.302.3.935

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Chronic Self-Administration of Nicotine in Rats Impairs T Cell Responsiveness

Roma Kalra, Shashi P. Singh, Dean Kracko, Shannon G. Matta, Burt M. Sharp and Mohan L. Sopori
Journal of Pharmacology and Experimental Therapeutics September 1, 2002, 302 (3) 935-939; DOI: https://doi.org/10.1124/jpet.302.3.935
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