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 Ca(2+)-dependent mechanisms. The aim of the present study was to determine whether the effects of methotrexate are mediated by a direct action on cellular Ca(2+) fluxes. Methotrexate did not affect the ATP-dependent (45)Ca(2+) uptake by mitochondria, microsomes and inside-out plasma membrane vesicles and Ca(2+) efflux from plasma membrane vesicles. However, methotrexate was able to stimulate (45)Ca(2+) release from preloaded microsomes. The amount of Ca(2+) released by methotrexate was similar to that induced by IP(3). Methotrexate could be acting through the capacitative calcium entry mechanism.
Pagadigorria
Clairce L S
CL
Laboratory of Biological Oxidations, Department of Biochemistry, University of Maringá, 87020900 Maringá, Brazil.
Marcon
Fernanda
F
Kelmer-Bracht
Ana M
AM
Bracht
Adelar
A
Ishii-Iwamoto
Emy L
EL
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002118:Calcium; D008727:Methotrexate