The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
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Calcium Signaling and c-Fos Gene Expression via M3 Muscarinic Acetylcholine Receptors in Human T- and B-Cells
Takeshi FujiiKoichiro Kawashima
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2000 Volume 84 Issue 2 Pages 124-132


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.

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© The Japanese Pharmacological Society 2000
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