Dual effect of spermine on mitochondrial Ca2+ transport.
1. A dual effect of the polyamine spermine on Ca2+ uptake by isolated rat liver, brain and heart mitochondria could be demonstrated by using a high-resolution system for studying mitochondrial Ca2+ transport. Depending on the experimental situation, spermine had an inhibiting or accelerating effects on mitochondrial Ca(2+)-uptake rate, but invariably increased the mitochondrial Ca2+ accumulation. 2. Both effects were concentration-dependent and clearly discernible on the basis of their different kinetic characteristics. For mitochondria from all three tissues the half-maximally effective concentration for inhibition of the initial rate of Ca2+ uptake was approx. 180 microM, whereas that for the subsequent stimulation of Ca2+ accumulation was approx. 50 microM. 3. Acceleration of the initial uptake rate could be seen when the mitochondria were preloaded with spermine during a 2 min preincubation period and thereafter incubated in a medium without spermine. 4. When such spermine-preloaded mitochondria were incubated in a spermine-containing medium, the increase in Ca(2+)-accumulation capacity was maintained in spite of an unchanged rate of Ca2+ uptake. 5. Mg2+ interacted with the effects of spermine in a differential manner, enhancing the initial inhibition of the rate of mitochondrial Ca2+ uptake and diminishing the subsequent stimulation of mitochondrial Ca2+ accumulation. 6. This dual effect of spermine on mitochondrial Ca2+ transport resolves the apparent paradox that a polycationic compound can act as a stimulator of Ca2+ uptake.
Lenzen
S
S
Institute of Pharmacology and Toxicology, University of Göttingen, Federal Republic of Germany.
Münster
W
W
Rustenbeck
I
I
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013096:Spermine / Q000502:physiology*
D002413:Cations, Divalent; D013096:Spermine; D008274:Magnesium; D002118:Calcium