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

概要

論文の詳細を見る
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.
公益社団法人日本薬理学会の論文
2000-10-01