Properties of a new calcium ion antagonist on cellular uptake and mitochondrial efflux of calcium ions.
Compound YS 035 [NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine] is a new synthetic compound capable of inhibiting Ca2+ uptake by different cells. The inhibition of Ca2+ uptake by muscle cells isolated from chicken embryo is dose-dependent in the compound YS 035 concentration range 10-30 microM. The new compound also inhibits Ca2+ entry into rat brain synaptosomes and less effectively into baby-hamster kidney cells. Compound YS 035 partially inhibits the slow Ca2+ release induced by Ruthenium Red and the rapid Na+-dependent efflux from heart mitochondria. The inhibition of the Na+/Ca2+ exchange appears to be of a non-competitive type with an apparent Ki of 28 microM. The new Ca2+ antagonist totally inhibits the Ca2+ efflux from liver mitochondria induced by Ruthenium Red, but it does not affect the release induced by uncoupler, respiratory inhibitor or chelator, nor the mitochondrial ATP synthesis and membrane potential. The properties shown by the new compound indicate it to be a Ca2+ antagonist and a useful tool for studies on the mitochondrial Ca2+ transport.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D002642:Chick Embryo; D006224:Cricetinae; D005260:Female; D007668:Kidney / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013094:Spermatozoa / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D002121:Calcium Channel Blockers; D010627:Phenethylamines; C041094:N,N-bis(3,4-dimethoxyphenethyl)-N-methylamine; D002118:Calcium