头上腺素受体的进化和分歧:为什么有时"药物不起作用"在鱼类中
William Joyce1, Jim Warwicker2, Holly A Shiels3
1Department of Biology - Zoophysiology, Aarhus University, 8000 Aarhus C, Denmark.
The Journal of experimental biology
|October 12, 2023
概括
鱼类中的上腺素受体 (AR) 与哺乳动物具有显著的进化差异. 这些区别影响了药物开发,需要针对远距离上腺素信号的定制研究方法.
科学领域:
- 进行比较的基因组学.
- 进化生物学是进化的生物学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 上腺素受体 (ARs) 调节脊椎动物的重要生理功能.
- 远鱼是研究上腺体调节的关键模型.
- 哺乳动物衍生药理学剂是常用的,但可能不适合鱼类.
研究的目的:
- 为了审查上腺体受体 (ARs) 的进化史在远程.
- 为了突出与哺乳动物和其他脊椎动物相比,遥远的AR的跨物种差异.
- 为了强调研究鱼类ARs由于异常药理学的挑战.
主要方法:
- 对ARs的遗传学和比较基因组分析.
- 远距离的ARs的结构建模,以预测连带结合.
- 关于鱼类ARs的药理学研究的文献综述.
- 结合分子遗传学和药理学 (肝脏,心脏,红细胞) 的案例研究.
主要成果:
- 远距离的ARs由于基因重复和损失而表现出与哺乳动物的显著基因组和进化区别.
- 结构建模表明,teleost和哺乳动物ARs之间的连接物结合亲和力有差异.
- 与哺乳动物标准相比,鱼类ARs经常显示非典型的药理反应.
- 结合分子和药理学方法,提高了在特定的teleost组织中AR表达的理解.
结论:
- 进化差异为研究远程生物中的上腺体信号发送带来了独特的挑战.
- 哺乳动物药理学并不总是适用于鱼类ARs.
- 未来的研究将"omics"技术与古典药理学结合起来,对于推进teleost上腺激素信号研究至关重要.
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