Ca2+ uptake and energy supply of sheep heart mitochondria in presence of some calcium antagonists.
The action of the calcium antagonists nifedipine, bepridil, diltiazem and of an alpha adrenergic antagonist, prazosin, was studied on Ca2+ uptake and energy supply (i.e. oxidative phosphorylation) of sheep heart mitochondria. In order to appreciate an inhibition, uncoupler like, of the Ca2+ influx, a comparative study was made with DNP. The Ca2+ uptake was inhibited, at the concentrations tested, (less than or equal to 10(-3) M), only by bepridil, nifedipine and DNP: a 2.5.10(-4) M concentration of these drugs brought an inhibition of 95%, 65% and 100% respectively. The inhibition was accompanied by a decrease of the ADP:O ratio and the RCI except with nifedipine. It is suggested that bepridil could act more as an inhibitor-uncoupler and nifedipine as an inhibitor of the Ca2+ uptake uniporter; both leading to a decrease of the mitochondrial participation in the regulation of the cellular homeostasis. This phenomenon could contribute to the known clinical properties of bepridil and nifedipine.
D000818:Animals; D015764:Bepridil; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012756:Sheep
D002121:Calcium Channel Blockers; D011759:Pyrrolidines; D015764:Bepridil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium; D011224:Prazosin