We previously reported that intraerythrocytic
malaria parasites have their development synchronized by
melatonin and other products of
tryptophan catabolism (i.e.
serotonin,
N-acetylserotonin and
tryptamine). Here, we show that N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (
AFMK), a product of
melatonin degradation, synchronizes Plasmodium chabaudi and Plasmodium falciparum. The synchronization is abrogated with a
melatonin receptor antagonist,
luzindole. We established quantitatively that a differential
AFMK production occurred within the intraerythrocytic stages of rodent
malaria parasite Plasmodium chabaudi (ring, trophozoite and schizont), when the infected erythrocytes were previously incubated with
melatonin. Measurement of
AFMK formation in P. chabaudi after incubation with
melatonin at a concentration of 500 nmol/L revealed the following values for
AFMK production: ring 0.1 +/- 0.1 nmol/L, trophozoite 22.9 +/- 0.5 nmol/L, schizont 29 +/- 5 nmol/L. Confocal and spectrofluorophotometer experiments with isolated parasites and infected-RBC, loaded with
calcium indicator Fluo-4 showed that
AFMK elicits an increase in the cytosol
calcium concentration in these parasites. Our data suggest that
AFMK could have an important role in modulating the cell cycle of
malaria parasites mainly in the late stages (trophozoite and schizont).