Calcium Signaling and c-Fos Gene Expression via M_3 Muscarinic Acetylcholine Receptors in Human T-and B-Cells

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We previously showed that blood acetylcholine(ACh)originates mainly from T−lymphocytes, and that stimulation of muscarinic ACh receptors(mAChRs)induces Ca<SUP>2+</SUP> oscillations and up−regulates c−fos gene expression in both T− and B−lymphocytes.In the present study, we investigated which mAChR subtypes are involved in Ca<SUP>2+</SUP> signaling and c−fos gene expression in human T−(CEM)and B−(Daudi)cells.Stimulation of mAChRs with 100μM oxotremorine−M, an M<SUB>1</SUB>/M<SUB>3</SUB> agonist, increased levels of intracellular free Ca<SUP>2+</SUP>([Ca<SUP>2+</SUP>]<SUB>i</SUB>)and c−fos mRNA expression in both cell lines.4−DAMP, an M<SUB>3</SUB> antagonist, more effectively blocked the oxotremorine−M−induced increase in [Ca<SUP>2+</SUP>]<SUB>i</SUB> than pirenzepine and telenzepine, M<SUB>1</SUB>−receptor antagonists;AF−DX 116, an M<SUB>2</SUB> antagonist;hexahydrosiladifenidol, a weak M<SUB>3</SUB> antagonist;or hexamethonium and d−tubocurarine, nicotinic receptor antagonists.McN−A−343(100μM), a partial M<SUB>1</SUB>−receptor agonist, had no apparent effect on [Ca<SUP>2+</SUP>]<SUB>i</SUB> in either cell line.The oxotremorine−M−induced up−regulation of c−fos transcription was inhibited by 4−DAMP, but not by pirenzepine or AF−DX 116.Our findings thus suggest that ACh released from T−lymphocytes acts as an autocrine/paracrine factor, transmitting a Ca<SUP>2+</SUP>−dependent signal to the nuclei of T− and B−lymphocytes via M<SUB>3</SUB> receptors.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 84(2), 124-132, 2000-10-01

    公益社団法人 日本薬理学会

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各種コード

  • NII論文ID(NAID)
    10008185481
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    5549167
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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