Caffeine-stimulated Ca2+ release from the intracellular stores of hepatocytes is not mediated by ryanodine receptors.

Caffeine has been much used to examine the possibility that ryanodine receptors similar to those found in skeletal and cardiac muscle may be more widely distributed and perhaps contribute to regenerative Ca2+ signals in electrically inexcitable cells. In permeabilized hepatocytes loaded with 45Ca2+, caffeine (> or = 5 mM) decreased the 45Ca2+ content of the intracellular stores by up to 60%; the effect was substantially reversible and it was not mimicked by the closely related methylxanthine theophylline (20 mM). Ryanodine (5 microM) stimulated a far smaller Ca2+ mobilization (7 +/- 1%). Procaine (1 mM), Ruthenium Red (10 microM) and ryanodine (5 microM) did not affect the Ca2+ release evoked by InsP3 (3 microM) or caffeine (30 mM). We conclude that caffeine can specifically cause Ca2+ release from the intracellular stores of hepatocytes, but the effect is unlikely to be mediated by ryanodine receptors.