Effect of antimalarial drugs on rat enterocyte mitochondrial phospholipase D activity.
We have earlier shown that enterocyte mitochondria contain a phospholipase D (PLD) activity which can be stimulated by oxygen free radicals, divalent cations and polyamines. The functional significance of this enzyme in mitochondria is not known but it can be investigated using selective inhibitors. In the present study, mitochondrial PLD was activated by exposure to oxidants (X+XO or menadione), calcium or polyamines and the effect of antimalarial drugs, chloroquine, amodiaquin and primaquine on PLD activity was studied. Chloroquine and amodiaquine inhibited Ca2+ stimulated PLD activity in dose dependent manner whereas these drugs had no significant effect on PLD activated by oxidants or polyamines. Increasing the calcium concentration relieved the PLD inhibition by these drugs. Primaquine did not have any effect on calcium stimulated PLD activity whereas it slightly activated the enzyme. These results indicate that chloroquine and amodiaquine may bind with calcium making it unavailable for PLD activation.
Madesh
M
M
Department of Gastrointestinal Sciences, Christian Medical College Hospital, Vellore, India.
Balasubramanian
K A
KA
D000655:Amodiaquine / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004789:Enzyme Activation; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D016877:Oxidants / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D011319:Primaquine / Q000494:pharmacology; D051381:Rats
D000962:Antimalarials; D016877:Oxidants; D010712:Phosphatidic Acids; D010714:Phosphatidylethanolamines; D011073:Polyamines; D000655:Amodiaquine; D002738:Chloroquine; D010739:Phospholipase D; D011319:Primaquine; D002118:Calcium