Prostaglandins stimulate calcium-linked changes in heart mitochondrial respiration

Abstract

This study was done to determine the influence of prostaglandins (PGs) on oxidative phosphorylation and Ca-related changes in cardiac mitochondria. For most of the experiments mitochondria were isolated by using a nagarse-homogenization combination method that yields both subsarcolemmal and interfibrillar populations. When Ca (30-420 microM) was added a progressive stimulation in resting respiration was observed. Similarly, preaddition of Ca inhibited subsequent oxidative phosphorylation when ADP was added to the same preparation. The effect of calcium was enhanced by pretreating mitochondria with PGs E2, F2 alpha, and I2 (prostacyclin). Three PG concentrations, 100 pg/ml, 1 ng/ml, and 10 ng/ml were evaluated. For the most part the effect of PGs was concentration dependent with the exception of PGE2, which showed no effect at the highest concentration. The effects of PGs were observed when both NADH (pyruvate-malate) and succinate-linked respiratory substrates were used. Similar effects were evident when mitochondria were harvested using a non-nagarse homogenization method that yields a primarily subsarcolemmal population, although this preparation exhibited substantially higher sensitivity to Ca. None of the PGs had any direct effect on either resting respiration rate or oxidative phosphorylation in the absence of Ca, irrespective of isolation procedure or choice of substrate. The study demonstrates that PGs can augment Ca-related changes in cardiac mitochondrial respiration through an as yet unknown mechanism. The results may be important in understanding the role of endogenously synthesized PGs in cardiac pathology associated with defective intracellular Ca homeostasis.