The effects of calmodulin (CaM) and CaM antagonists on microsomal Ca2+ release through a ryanodine-sensitive mechanism were investigated in rat pancreatic acinar cells. When caffeine (10 mM) was added after a steady state of ATP-dependent 45Ca2+ uptake into the microsomal vesicles, the caffeine-induced 45Ca2+ release was significantly increased by pretreatment with ryanodine (10 μM). The presence of W-7 (60 μM), a potent inhibitor of CaM, strongly inhibited the release, while W-5 (60 μM), an inactive CaM antagonist, showed no inhibition. Inhibition of the release by W-7 was observed at all caffeine concentrations (5-30 mM) tested. The presence of exogenously added CaM (10 μg/ml) markedly increased the caffeine (5-10 mM)-induced 45Ca2+ release and shifted the dose-response curve of caffeine-induced 45Ca2+ release to the left. Cyclic ADP-ribose (cADPR, 2 μM)-induced 45Ca2+ release was enhanced by the presence of ryanodine (10 μM). cADPR (2 μM)- or ryanodine (500 μM)-induced 45Ca2+ release was also inhibited by W-7 (60 μM), but not by W-5 (60 μM), and was stimulated by CaM (10 μg/ml). These results suggest that the ryanodine-sensitive Ca2+ release mechanism of rat pancreatic acinar cells is modulated by CaM.
Ozawa, T. (1999). Ryanodine-sensitive Ca2+ release mechanism of rat pancreatic acinar cells is modulated by calmodulin. Biochimica et Biophysica Acta - Molecular Cell Research, 1452(3), 254–262. https://doi.org/10.1016/S0167-4889(99)00135-4