Takeshi Fujii and Koichiro Kawashima*
Department of Pharmacology, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen,
Minato-ku, Tokyo 105-8512, Japan
*Corresponding author.ﾊﾊ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 100ﾊmM 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ﾊ116,
an M2 antagonist; hexahydrosiladifenidol, a weak M3
antagonist; or hexamethonium and d-tubocurarine, nicotinic receptor
antagonists. McN-A-343 (100ﾊmM), 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ﾊ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.
Keywords: Acetylcholine, Calcium, c-Fos, Lymphocyte, Muscarinic receptor
Copyrightｩ The Japanese Pharmacological Society 2000
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