Iron and transition metal transport into erythrocytes mediated by nifedipine degradation products and related compounds.
The aim of this investigation was to determine the mechanism of action of the nitrosophenylpyridine derivative of nifedipine ("nitrosonifedipine", NN) on Fe(II) transport into erythrocytes. Nifedipine is rapidly degraded to NN by daylight. We used rabbit erythrocytes, NN, and several chemically related substances, and examined their effects on the transfer of iron and other transition metals (cadmium, cobalt, manganese, nickel, zinc) into and out of the cells. NN mediated the transfer of iron and zinc but not the other metals into the cell cytosol. The transfer of Fe(II) was not affected by changes in cell membrane potential and could not be ascribed to free radical production. Two hydroxamic acid compounds chemically related to NN also stimulated iron and zinc uptake, but no evidence was obtained for cell-induced transformation of NN to them. In vivo, NN is probably converted to a lactam derivative. This compound was found to have no effect on iron uptake by the cells. It is concluded that NN has a relatively high specificity for the transport of iron compared with other transition metals, and small changes in its structure markedly affect this action. Also, because the lactam to which NN is converted in vivo is inactive, it is unlikely that nifedipine will affect iron metabolism after therapeutic administration.
Savigni
Donna L
DL
Department of Physiology, The University of Western Australia, 35 Stirling Highway, Crawley, Australia.
Wege
Dieter
D
Cliff
Garth S
GS
Meesters
Mark L H
ML
Morgan
Evan H
EH
D000818:Animals; D001673:Biodegradation, Environmental; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D007501:Iron / Q000097:blood*; D007700:Kinetics; D008670:Metals / Q000097:blood*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D008670:Metals; D007501:Iron; D009543:Nifedipine