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

Abstract

Our earlier observations suggest that M₃ muscarinic acetylcholine (ACh) receptors (mAChRs) are involved in Ca²⁺ signaling and regulation of c-fos gene expression in T lymphocytes. Here, we describe the effects of YM905, a novel M₃ 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 μM oxotremorine-M, an M₁/M₃ agonist (IC₅₀=100 nM), and also inhibited 10 μM oxotremorine-M-induced upregulation of c-fos gene expression at 1 μM. These findings demonstrate that YM905 antagonizes the intracellular responses in T cells induced via mAChRs, possibly M₃ receptors.