Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito
Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito
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DOI：
10.1038/32667
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发表时间：
1998-03-19
期刊：
影响因子：
64.8
通讯作者：
Morris, HR
中科院分区：
文献类型：
--
作者：
Billker, O;Lindo, V;Morris, HR
疟疾通过称为配子细胞的成熟有性血液生活阶段从脊椎动物宿主传播到蚊子媒介(1,2)。在摄入蚊子血粉后的几秒钟内，配子细胞就会进行配子发生。诱导需要同时暴露于至少两种体外刺激：血粉温度下降至比脊椎动物宿主温度低 5°C(1-3)，pH 值从 7.4 上升至 8.0-8.2（参考文献 1、4）。在体内，蚊子血粉的 pH 值在 7.5 和 7.6 之间（参考文献 5、6）。据认为，体内第二诱导剂是一种未知的蚊源配子体激活因子(5,7,8)。在这里我们表明这个因子是黄嘌呤酸。我们还表明，低浓度的黄嘌呤酸可以与 pH 一起作用，在体外诱导配子发生。结构相关的化合物在体外诱导配子发生方面的效果至少低九倍。在色氨酸代谢的犬尿氨酸途径（黄尿酸是其副产物）中存在损伤的果蝇突变体中，在粗昆虫匀浆中没有检测到替代活性化合物。这些数据可以为合理开发使用药物或新的难治性蚊子基因型来阻止寄生虫配子发生来阻断疟疾传播的新方法奠定基础。
Malaria is transmitted from vertebrate host to mosquito vector by mature sexual blood-living stages called gametocytes(1,2). Within seconds of ingestion into the mosquito bloodmeal, gametocytes undergo gametogenesis. Induction requires the simultaneous exposure to at least two stimuli in vitro: a drop in bloodmeal temperature to 5 degrees C below that of the vertebrate host(1-3), and a rise in pH from 7.4 to 8.0-8.2 (refs 1, 4). In vivo the mosquito bloodmeal has a pH of between 7.5 and 7.6 (refs 5, 6). It is thought that in vivo the second inducer is an unknown mosquito-derived gametocyte-activating factor(5,7,8). Here we show that this factor is xanthurenic acid. We also show that low concentrations of xanthurenic acid can act together with pH to induce gametogenesis in vitro. Structurally related compounds are at least ninefold less effective at inducing gametogenesis in vitro. In Drosophila mutants with lesions in the kynurenine pathway of tryptophan metabolism (of which xanthurenic acid is a side product), no alternative active compound was detected in crude insect homogenates. These data could form the basis of the rational development of new methods of interrupting the transmission of malaria using-drugs or new refractory mosquito genotypes to block parasite gametogenesis.