Olfactory receptor 78 participates in carotid body response to a wide range of low O2 levels but not severe hypoxia
Olfactory receptor 78 participates in carotid body response to a wide range of low O2 levels but not severe hypoxia
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DOI：
10.1152/jn.00075.2020
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发表时间：
2020-05-01
影响因子：
2.5
通讯作者：
Prabhakar, Nanduri R.
中科院分区：
文献类型：
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作者：
Peng, Ying-Jie;Gridina, Anna;Prabhakar, Nanduri R.
观察了嗅觉受体78（Olfr 78）在颈动脉体（CB）缺氧反应中的作用。具有Olfr 78的整体缺失的BL 6小鼠表现出受损的缺氧性反应（HVR），这是CB化学感觉反射、CB感觉神经活动的标志。降低血管球细胞内Ca ~（2+）浓度（[Ca ~（2+）]（i））对缺氧（PO_2接近40 mmHg）的反应。相比之下，严重缺氧（PO 2类似于10 mmHg）抑制呼吸，并产生非常弱的CB感觉神经兴奋，但在Olfr 78无效球细胞中[Ca 2 +]（i）显著升高。由Olfr 78配体、乳酸盐诱发的CB感觉神经兴奋。丙酸、乙酸和丁酸在突变小鼠中不受影响，并且小于由缺氧引起的（PO 2类似于40 mmHg）。在JAX遗传背景的Olfr 78缺失小鼠中获得了类似的结果。这些结果证明了Olfr 78在CB对大范围缺氧的反应中的作用，但不是严重缺氧，并且不需要乳酸或任何其他短链脂肪酸。新的和值得注意的是目前的研究表明，嗅觉受体78（Olfr 78），一种G蛋白偶联受体，是颈动脉体对大范围低氧水平的缺氧传感机制的组成部分，而不是严重缺氧，并且Olfr 78参与不需要乳酸或任何其他短链脂肪酸，Olfr 78的建议配体。
The role of olfactory receptor 78 (Olfr78) in carotid body (CB) response to hypoxia was examined. BL6 mice with global deletion of Olfr78 manifested an impaired hypoxic ventilatory response (HVR), a hallmark of the CB chemosensory reflex, CB sensory nerve activity. and reduced intracellular Ca2+ concentration ([Ca2+](i); ) response of glomus cells to hypoxia (PO2 similar to 40 mmHg). In contrast, severe hypoxia (PO2 similar to 10 mmHg) depressed breathing and produced a very weak CB sensory nerve excitation but robust elevation of [Ca2+](i) ; in Olfr78 null glomus cells. CB sensory nerve excitation evoked by Olfr78 ligands, lactate. propionate, acetate, and butyrate were unaffected in mutant mice and were smaller than that evoked by hypoxia (PO2 similar to 40 mmHg). Similar results were obtained in Olfr78 null mice on a JAX genetic background. These results demonstrate a role for Olfr78 in CB responses to a wide range of hypoxia, but not severe hypoxia, and do not require either lactate or any other short-chain fatty acids.NEW & NOTEWORTHY The current study demonstrates that olfactory receptor 78 (Olfr78), a G protein-coupled receptor, is an integral component of the hypoxic sensing mechanism of the carotid body to a wide range of low oxygen levels, but not severe hypoxia, and that Olfr78 participation does not require either lactate or any other short-chain fatty acids, proposed ligands of Olfr78.