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- W1992857103 abstract "This study was carried out to define the effects of various Ca2+ channel modulatory drugs on mitochondrial Ca2+ movements. Bovine adrenal medulla mitochondria took up Ca2+ at an initial rate of 6.8 nmol mg protein−1 5 s−1, with a Km of 15 μM and a Bmax of 30 nmol mg protein−1. At 30 μM, neither verapamil, diltiazem, nitrendipine nor Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate] affected the initial rate of Ca2+ uptake. Ca2+-loaded mitochondria retained their Ca2+ contents in the presence of ruthenium red for at least 30 min. Cinnarizine and flunarizine, but not verapamil, diltiazem, isradipine, Bay K 8644 or nitrendipine, caused a fast and dramatic Na+-independent Ca2+ loss. Other Ca2+ channel antagonists assayed such as penfluridol, R56865 [N-[1-(4-(4-fluorophenoxy)butyl)]-4-piperidinyl-N-methyl-2-benzothiazolamine], lidoflazine, R87926 [(+)-(S)-4-(2-benzothiazolyl-methylamino)-α-[(3,4-difluorophenoxy) methyl] 1 piperidine] and sabeluzole, also had a mitochondrial Ca2+ depleting effect which seemed to be directly related to their octanol/water partition coefficient. The Na+-dependent Ca2+ efflux from mitochondria was completely inhibited by diltiazem and greatly blocked by nitrendipine. Isradipine caused a moderate blockade and Bay K 8644 and verapamil had no effect. All these data open the possibility of developing novel Ca2+ channel antagonists having selective actions on plasmalemmal Ca2+ channels, and others with additional and different effects on mitochondrial Ca2+ transport. Mitochondria act as a Ca2+ sink in pathological ischemic conditions when there is an abnormally high influx of Ca2+ into the cell. The prevention of mitochondrial Ca2+ overload, in addition to causing plasmalemmal Ca2+ channel blockade, might be an important contributing factor to the therapeutic profile of those Ca2+ channel antagonists in the treatment of tissue ischemic diseases." @default.
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- W1992857103 date "1995-03-01" @default.
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- W1992857103 title "Effects of Ca2+ channel antagonist subtypes on mitochondrial Ca2+ transport" @default.
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- W1992857103 doi "https://doi.org/10.1016/0922-4106(95)90170-1" @default.
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