[Effect of caffeine and cyclosporin A on the transmembrane exchange of Ca ions in smooth muscle mitochondria].
The effects of cyclosporin A and caffeine on the active and passive transport of Ca2+ in mitochondria isolated from adult rat myometrium were studied by fluorescent technique using Ca2+-sensitive probe tetracycline (TC). It was shown that 5 microM cyclosporin increases Ca2+ accumulation by the mitochondria matrix. But it fails to exhibit such effect when 20 mM caffeine was also present in the incubation medium, while the inhibitory action of caffeine on the accumulation of Ca2+ reveals nevertheless in the absence or presence of cyclosporin A. In case of the preliminary incubation of mitochondria with 10 mM caffeine before the initiation of transport process one could also observe the inhibition of kinetic parameters of the active accumulation of Ca2+ by the mitochondria. It was also shown, that caffeine stimulates passive efflux of Ca2+ from the myometrium mitochondria. Thus we conclude, that the stimulating effect of cyclosporin on Ca2+ accumulation by the myometrium mitochondria is sensitive to caffeine, while caffeine has no direct effect on Ca2+-uniporter, but it evidently disturbs the barrier function of the inner mitochondria membrane in such way, that stimulating effect of cyclosporin A cannot develop.
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000037:antagonists & inhibitors; D007700:Kinetics; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D002110:Caffeine; D016572:Cyclosporine; D002118:Calcium