title: Multiple effects of caffeine on Ca2+ release and influx in human B lymphocytes.
abstract: Caffeine has been used as a pharmacological tool to study the ryanodine receptor (RYR)-mediated Ca2+ release from caffeine-sensitive, inositol 1,4,5,-trisphosphate (IP3)-insensitive pools. In the present study, we demonstrate multiple effects of caffeine on Ca2+ homeostasis in human B lymphocytes. Although B cells express a functional RYR, which can be activated by 4-chloro-m-cresol following depletion of IP(3)-sensitive pools, caffeine does not activate RYR-mediated Ca2+ release. Instead, caffeine dose-dependently inhibited IP3 receptor (IP3R)-mediated Ca2+ release, RYR-mediated Ca2+ release and B cell receptor-initiated Ca2+ influx, while high concentrations of caffeine (> or = 25 mM) induced a Ca2+ influx. In contrast with its ability to suppress receptor-stimulated Ca2+ influx, caffeine had no significant effect on the store-operated Ca2+ (SOC) channel-dependent Ca2+ influx induced by thapsigargin. Thus, caffeine may act as an inhibitor on a single or multiple site(s) responsible for regulating the IP3R channel, RYR channel and presumably the receptor-mediated SOC channel. The present report may be the first demonstration of multiple effects of caffeine on Ca2+ mobilization in single cell type. Our results suggest the need for caution regarding use of caffeine simply as a RYR-activator to study Ca2+ homeostasis in eucaryotic cells.
authors.affiliation: Department of Anesthesiology, Uniformed Services University of The Health Sciences, Bethesda, MD 20814-4799, USA. ysei@usuhs.mil
authors.forename: Y
authors.initials: Y
authors.lastname: Sei
authors.forename: K L
authors.initials: KL
authors.lastname: Gallagher
authors.forename: J W
authors.initials: JW
authors.lastname: Daly
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D002118:Calcium