Dk. Muhia et al., The gametocyte-activating factor xanthurenic acid stimulates an increase in membrane-associated guanylyl cyclase activity in the human malaria parasite Plasmodium falciparum, MOL MICROB, 42(2), 2001, pp. 553-560
Sex is an obligate step in the life cycle of the malaria parasite and occur
s in the midgut of the mosquito vector. With both Plasmodium falciparum and
Plasmodium berghei, the tryptophan metabolite xanthurenic acid induces the
release of motile male gametes from red blood cells (exflagellation), a pr
erequisite for fertilization. The addition of cGMP or phosphodiesterase inh
ibitors to cultures of mature gametocytes has also been shown to stimulate
exflagellation. Here, we demonstrate that there is a guanylyl cyclase activ
ity associated with mature P. falciparum, gametocyte membrane preparations,
which is dependent on the presence of Mg2+/Mn2+ but is inhibited by Ca2+.
Significantly, this activity is increased on addition of xanthurenic acid.
In contrast, a xanthurenic acid precursor (3-hydroxykynurenine), which is n
ot an inducer of exflagellation, does not induce this guanylyl cyclase acti
vity. These results therefore suggest that xanthurenic acid-induced exflage
llation may be mediated by activation of the parasite cGMP signalling pathw