Calcium Signaling and c-Fos Gene Expression via M3 Muscarinic Acetylcholine Receptors in Human T- and B-Cells.

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  • Fujii Takeshi
    Department of Pharmacology,Kyoritsu College of Pharmacy,1-5-30 Shibakoen,Minato-ku,Tokyo 105-8512,Japan
  • Kawashima Koichiro
    Department of Pharmacology,Kyoritsu College of Pharmacy,1-5-30 Shibakoen,Minato-ku,Tokyo 105-8512,Japan

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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 Ca2+ 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 Ca2+ signaling and c−fos gene expression in human T−(CEM)and B−(Daudi)cells.Stimulation of mAChRs with 100μM oxotremorine−M, an M1/M3 agonist, increased levels of intracellular free Ca2+([Ca2+]i)and c−fos mRNA expression in both cell lines.4−DAMP, an M3 antagonist, more effectively blocked the oxotremorine−M−induced increase in [Ca2+]i than pirenzepine and telenzepine, M1−receptor antagonists;AF−DX 116, an M2 antagonist;hexahydrosiladifenidol, a weak M3 antagonist;or hexamethonium and d−tubocurarine, nicotinic receptor antagonists.McN−A−343(100μM), a partial M1−receptor agonist, had no apparent effect on [Ca2+]i 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 Ca2+−dependent signal to the nuclei of T− and B−lymphocytes via M3 receptors.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 84 (2), 124-132, 2000

    公益社団法人 日本薬理学会

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