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 IP3-sensitive pools, caffeine does not activate RYR-mediated Ca2+release. Instead, caffeine dose-dependently inhibited IP3receptor (IP3R)-mediated Ca2+release, RYR-mediated Ca2+release and B cell receptor-initiated Ca2+influx, while high concentrations of caffeine (≥ 25mM) 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.