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


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

Takeshi Fujii and Koichiro Kawashima*

Department of Pharmacology, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan
*Corresponding author.FAX:+81-3-5400-2698
E-mail: kawashima-ki@kyoritsu-ph.ac.jp


Abstract: 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 100mM 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-DX116, an M2 antagonist; hexahydrosiladifenidol, a weak M3 antagonist; or hexamethonium and d-tubocurarine, nicotinic receptor antagonists. McN-A-343 (100mM), 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-DX116. 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.

Keywords: Acetylcholine, Calcium, c-Fos, Lymphocyte, Muscarinic receptor


Copyright The Japanese Pharmacological Society 2000

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