Caffeine inhibits agonists-induced cytoplasmic Ca2+ oscillations in single rat hepatocytes

Single hepatocytes microinjected with aequorin generate free Ca oscillations when stimulated by agonists such as phenylephrine or vasopressin. Here we show that caffeine by itself does not elicit any significant change in free Ca, nor it does lower the threshold concentration of an agonist needed to induced spikes. In contrast, both caffeine and theophylline inhibit agonist-induced spikes. Since ryanodine inhibits vasopressin-induced spikes, but not phenylephrine-induced spikes, the actions of caffeine probably involve another target than the ryanodine receptor. This antagonistic action of caffeine on the hepatocyte calcium oscillator agrees with an inhibitory action of caffeine on the receptor for inositol 1,4,5-triphosphate.