YM905, a novel M3 antagonist, inhibits Ca2+ signaling and c-fos gene expression mediated via muscarinic receptors in human T cells

Our earlier observations suggest that M-3 muscarinic acetylcholine (ACh) receptors (mAChRs) are involved in Ca2+ signaling and regulation of c fns gene expression in T lymphocytes. Here, we describe the effects of YM905, a novel M-3 antagonist, on evoked Ca2+ signaling and c-fos gene expression in CEM human leukemic T cells. YM905 significantly inhibited increases in intracellular free Ca2+ evoked by 10 muM oxotremorine-M, an M-1/M-3 agonist (IC50 = 100 nM), and also inhibited 10 muM oxotremorine-M-induced upregulation of c fns gene expression at 1 muM. These findings demonstrate that YM905 antagonizes the intracellular responses in T cells induced via mAChRs, possibly M-3 receptors. (C) 2001 Elsevier Science Inc. All rights reserved.