PMID- 28546857 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 2045-3701 (Print) IS - 2045-3701 (Electronic) IS - 2045-3701 (Linking) VI - 7 DP - 2017 TI - Chloroquine inhibits Ca(2+) permeable ion channels-mediated Ca(2+) signaling in primary B lymphocytes. PG - 28 LID - 10.1186/s13578-017-0155-5 [doi] LID - 28 AB - BACKGROUND: Chloroquine, a bitter tastant, inhibits Ca(2+) signaling, resulting in suppression of B cell activation; however, the inhibitory mechanism remains unclear. RESULTS: In this study, thapsigargin (TG), but not caffeine, induced sustained intracellular Ca(2+) increases in mouse splenic primary B lymphocytes, which were markedly inhibited by chloroquine. Under Ca(2+)-free conditions, TG elicited transient Ca(2+) increases, which additionally elevated upon the restoration of 2 mM Ca(2+). The former were from release of intracellular Ca(2+) store and the latter from Ca(2+) influx. TG-induced release was inhibited by 2-APB (an inhibitor of inositol-3-phosphate receptors, IP(3)Rs) and chloroquine, and TG-caused influx was inhibited by pyrazole (Pyr3, an inhibitor of transient receptor potential C3 (TRPC3) and stromal interaction molecule (STIM)/Orai channels) and chloroquine. Moreover, chloroquine also blocked Ca(2+) increases induced by the engagement of B cell receptor (BCR) with anti-IgM. CONCLUSIONS: These results indicate that chloroquine inhibits Ca(2+) elevations in splenic B cells through inhibiting Ca(2+) permeable IP(3)R and TRPC3 and/or STIM/Orai channels. These findings suggest that chloroquine would be a potent immunosuppressant. FAU - Wu, Yi-Fan AU - Wu YF AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Zhao, Ping AU - Zhao P AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Luo, Xi AU - Luo X AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Xu, Jin-Chao AU - Xu JC AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Xue, Lu AU - Xue L AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Zhou, Qi AU - Zhou Q AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Xiong, Mingrui AU - Xiong M AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Shen, Jinhua AU - Shen J AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Peng, Yong-Bo AU - Peng YB AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Yu, Meng-Fei AU - Yu MF AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Chen, Weiwei AU - Chen W AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Ma, Liqun AU - Ma L AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a FAU - Liu, Qing-Hua AU - Liu QH AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South Central University for Nationalities, Wuhan, 430074 China. ISNI: 0000 0000 9147 9053. GRID: grid.412692.a LA - eng PT - Journal Article DEP - 20170523 PL - England TA - Cell Biosci JT - Cell & bioscience JID - 101561195 PMC - PMC5442594 OTO - NOTNLM OT - B cells OT - Ca2+ OT - Chloroquine OT - IP3R OT - STIM/Orai channels OT - TRPC3 channels EDAT- 2017/05/27 06:00 MHDA- 2017/05/27 06:01 PMCR- 2017/05/23 CRDT- 2017/05/27 06:00 PHST- 2016/12/30 00:00 [received] PHST- 2017/05/19 00:00 [accepted] PHST- 2017/05/27 06:00 [entrez] PHST- 2017/05/27 06:00 [pubmed] PHST- 2017/05/27 06:01 [medline] PHST- 2017/05/23 00:00 [pmc-release] AID - 155 [pii] AID - 10.1186/s13578-017-0155-5 [doi] PST - epublish SO - Cell Biosci. 2017 May 23;7:28. doi: 10.1186/s13578-017-0155-5. eCollection 2017.