Effects of calcium antagonists on glycolysis of rat brain synaptosomes.
The effects of calcium antagonists nimodipine, nicardipine and flunarizine on lactate production and specific activities of some enzymes regulating glycolytic flux have been evaluated in synaptosomes isolated from rat whole brain and submitted to in vitro chemical hypoxia induced by rotenone, an inhibitor of mitochondrial respiration. The following enzymes have been tested; hexokinase (ATP: D-hexose-6-phosphotransferase, EC2.7.1.1), phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40). The results show that rotenone increases by about eight times the production of lactate; nicardipine and nimodipine, starting from a concentration of 10(-4) M, were able to counteract the rotenone-induced stimulation of glycolysis, but flunarizine was without effect. The dihydropyridines but not flunarizine decreased the maximum activity of phosphofructokinase. This effect was already detectable at a concentration of 10(-5) M. Neither hexokinase nor pyruvate kinase were affected by any of the drugs studied.
Dagani
F
F
Istituto di Farmacologia, Facoltà di Scienze MM.FF.NN, Università di Pavia, Italy.
Ferrari
R
R
Tosca
P
P
Canevari
L
L
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000378:metabolism; D007773:Lactates / Q000032:analysis; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000037:antagonists & inhibitors; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
D007773:Lactates; D012402:Rotenone; D009553:Nimodipine; D009529:Nicardipine; D006593:Hexokinase; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase; D005444:Flunarizine