Interactions between prostaglandin E 1 and calcium at the level of the mitochondrial membrane

Low concentrations of PGE₁ facilitate the exit of actively accumulated Ca²⁺ from rat liver mitochondria. The effect is evident at pH 6,4 and disappears at neutral pH. Ca²⁺ bound to the mitochondrial membrane in the absence of energy is not discharged by PGE₁.Under conditions that lead to its active accumulation, Ca²⁺ stimulates the binding of PGE₁ to mitochondria. The effect is concentration dependent (maximal at 500 μM Ca²⁺), is evident only at slightly acid pH, and is transitory. The binding of PGE₁ reaches a maximum between 30 sec and 2 min and then declines very rapidly, returning to the baseline 2–5 min after the addition of Ca²⁺. The maximal amount of PGE₁ bound is 1.3 nmoles per mg of mitochondrial protein, i.e., about 1% of the Ca²⁺ taken up by mitochondria. No PGE₁ is bound when permeant anions are tranported into mitochondria together with Ca²⁺. Sr²⁺ and Mn²⁺ also stimulate the binding of PGE₁.Aspirin and indomethacin are powerful inhibitors of the binding of PGE₁ to mitochondria. This effect appears to be secondary to the inhibition of mitochondrial Ca²⁺ transport by the antiinflammatory drugs.