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 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 microM oxotremorine-M, an M1/M3 agonist (IC50=100 nM), and also inhibited 10 microM oxotremorine-M-induced upregulation of c-fos gene expression at 1 microM. These findings demonstrate that YM905 antagonizes the intracellular responses in T cells induced via mAChRs, possibly M3 receptors.
Fujii
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minato-ku, 105-8512, Tokyo, Japan.
Kawashima
K
K
D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D016762:Genes, fos; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D000069464:Solifenacin Succinate; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D012333:RNA, Messenger; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D044005:Tetrahydroisoquinolines; D010095:Oxotremorine; C042743:oxotremorine M; D000069464:Solifenacin Succinate