Fluoxetine-resistant mutants in C-elegans define a novel family of transmembrane proteins
Fluoxetine-resistant mutants in C-elegans define a novel family of transmembrane proteins
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DOI：
10.1016/s1097-2765(00)80362-7
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发表时间：
1999-08-01
期刊：
影响因子：
16
通讯作者：
Thomas, JH
中科院分区：
文献类型：
--
作者：
Choy, RKM;Thomas, JH
氟西汀（百忧解）是一种抗抑郁药，被认为是通过阻断神经递质5 -羟色胺的突触前再摄取而起作用。尽管氟西汀在临床上广泛使用，但这种机制的直接证据很难在体内获得。我们已经确定氟西汀对秀丽隐杆线虫有额外的神经肌肉作用，这与抑制5 -羟色胺再摄取不同。通过筛选对这种效应有抗性的突变体，我们已经确定了7个基因。我们报告说，这些基因中的两个是同源的，并定义了一个新的基因家族，编码超过十二个多通跨膜蛋白。我们的发现可能对氟西汀的作用机制有临床意义。
Fluoxetine (Prozac) is an antidepressant that is thought to act by blocking presynaptic reuptake of the neurotransmitter serotonin. Despite widespread clinical use of fluoxetine, direct evidence for this mechanism has been difficult to obtain in vivo. We have determined that fluoxetine has an additional neuromuscular effect on C. elegans that is distinct from inhibition of serotonin reuptake. By screening for mutants resistant to this effect, we have identified seven genes. We report that two of these genes are homologous to each other and define a novel gene family that encodes over a dozen multipass transmembrane proteins. Our findings may have clinical implications for the mechanism of action of fluoxetine.