Effects of methotrexate on calcium flux in rat liver mitochondria, microsomes and plasma membrane vesicles

The metabolic effects of methotrexate in perfused livers are similar to those exerted by hormones acting through Ca2+-dependent mechanisms. The aim of the present study was to determine whether the effects of methotrexate are mediated by a direct action on cellular Ca2+ fluxes. Methotrexate did not affect the ATP-dependent 45Ca2+ uptake by mitochondria, microsomes and inside-out plasma membrane vesicles and Ca2+ efflux from plasma membrane vesicles. However, methotrexate was able to stimulate 45Ca2+ release from preloaded microsomes. The amount of Ca2+ released by methotrexate was similar to that induced by IP3. Methotrexate could be acting through the capacitative calcium entry mechanism.