Effects of phosphoenolpyruvate, other glycolytic intermediates and methylxanthines on calcium uptake by a mitochondrial fraction from rat pancreatic islets.
45Ca2+-accumulation by a mitochondrial fraction from isolated rat pancreatic islets was stronly stimulated by ATP. The ATP-dependent uptake was inhibited by phosphoenolpyruvate in a dose-dependent manner over a wide variety of conditions. Inhibition by phosphoenolpyruvate was non-completitive with respect to calcium, competitive with respect to magnesium, and antagonised by high Mg-ATP2- concentrations; fructose 1,6-diphosphate also decreased 45Ca2+-uptake. Other glucose metabolites were either less effective or ineffective in diminishing mitochondrial 45Ca2+-accumulation. The ATP-dependent uptake was also inhibited by xanthine derivatives (caffeine and 3-isobutyl-1-methylaxanthine) which potentiate the effects of glucose on insulin secretion. Cyclic AMP had no effect. It is thought that the rate of insulin secretion is a function of the cytosolic calcium concentration in the B-cell. These data show that phosphoenolpyruvate, fructose 1,6-diphosphate and methylxanthines might influence exocytosis by direct effects on mitochondrial calcium accumulation, and thus the intracellular distribution of calcium.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D006019:Glycolysis; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010728:Phosphoenolpyruvate / Q000494:pharmacology*; D051381:Rats; D014970:Xanthines / Q000494:pharmacology*
D014970:Xanthines; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D010728:Phosphoenolpyruvate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D008274:Magnesium; D002118:Calcium