Erythrocyte G protein-coupled receptor signaling in malarial infection
Erythrocyte G protein-coupled receptor signaling in malarial infection
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DOI：
10.1126/science.1089324
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发表时间：
2003-09-19
期刊：
影响因子：
56.9
通讯作者：
Haldar, K
中科院分区：
文献类型：
--
作者：
Harrison, T;Samuel, BU;Haldar, K
疟疾感染中涉及的红细胞机制知之甚少。我们已经发现，通过红细胞β 2-肾上腺素能受体和异源三聚体鸟嘌呤核苷酸结合蛋白（Galphas）的信号传导调节了人类恶性疟原虫的进入。刺激环腺苷3 '，5'-单磷酸产生的激动剂导致疟疾感染的增加，这可以被特异性受体拮抗剂阻断。此外，设计用于抑制Galphas蛋白功能的肽在体外减少恶性疟原虫培养物中的寄生虫血症，并且β-拮抗剂在体内小鼠模型中减少伯氏疟原虫感染的寄生虫血症。因此，通过红细胞β 2-肾上腺素能受体和Galphas的信号传导可以调节寄生虫物种之间的疟疾感染。
Erythrocytic mechanisms involved in malarial infection are poorly understood. We have found that signaling via the erythrocyte beta2-adrenergic receptor and heterotrimeric guanine nucleotide - binding protein (Galphas) regulated the entry of the human malaria parasite Plasmodium falciparum. Agonists that stimulate cyclic adenosine 3', 5'-monophosphate production led to an increase in malarial infection that could be blocked by specific receptor antagonists. Moreover, peptides designed to inhibit Galphas protein function reduced parasitemia in P. falciparum cultures in vitro, and beta-antagonists reduced parasitemia of P. berghei infections in an in vivo mouse model. Thus, signaling via the erythrocyte beta2-adrenergic receptor and Galphas may regulate malarial infection across parasite species.