Activation of the Carotid Body by Kappa Opioid Receptors Mitigates Fentanyl-Induced Respiratory Depression.

IF 5.1 Q2 CELL BIOLOGY
Ying-Jie Peng, Jayasri Nanduri, Ning Wang, Zheng Xie, Aaron P Fox, Nanduri R Prabhakar
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引用次数: 0

Abstract

Previous studies reported that opioids depress breathing by inhibiting respiratory neural networks in the brainstem. The effects of opioids on sensory inputs regulating breathing are less studied. This study examined the effects of fentanyl and sufentanil on carotid body neural activity, a crucial sensory regulator of breathing. Both opioids stimulated carotid body afferent nerve activity and increased glomus cell [Ca2+]i levels. RNA sequencing and immunohistochemistry revealed a high abundance of κ opioid receptors (KORs) in carotid bodies, but no µ or δ opioid receptors. A KOR agonist, like fentanyl, stimulated carotid body afferents, while a KOR antagonist blocked carotid body activation by fentanyl and KOR agonist. In unanesthetized rats, fentanyl initially stimulated breathing, followed by respiratory depression. A KOR agonist stimulated breathing without respiratory inhibition, and this effect was absent in carotid body-denervated rats. Combining fentanyl with a KOR agonist attenuated respiratory depression in rats with intact carotid body but not in carotid body-denervated rats. These findings highlight previously uncharacterized activation of carotid body afferents by fentanyl via KORs as opposed to depression of brainstem respiratory neurons by µ opioid receptors and suggest that KOR agonists might counteract the central depressive effects of opioids on breathing.

kappa阿片受体激活颈动脉体减轻芬太尼诱导的呼吸抑制。
先前的研究报道阿片类药物通过抑制脑干的呼吸神经网络来抑制呼吸。阿片类药物对调节呼吸的感觉输入的影响研究较少。这项研究检查了芬太尼和舒芬太尼对颈动脉体神经活动的影响,颈动脉体神经活动是呼吸的关键感觉调节器。两种阿片类药物均刺激颈动脉体传入神经活动并增加血管球细胞[Ca2+]i水平。RNA测序和免疫组化结果显示,颈动脉小体中κ类阿片受体(KORs)丰度高,但μ或δ类阿片受体不存在。像芬太尼一样,KOR激动剂刺激颈动脉体传入,而KOR拮抗剂通过芬太尼和KOR激动剂阻断颈动脉体激活。在未麻醉的大鼠中,芬太尼最初刺激呼吸,随后抑制呼吸。一种KOR激动剂刺激呼吸而无呼吸抑制,这种作用在颈动脉体去神经大鼠中不存在。芬太尼联合KOR激动剂可减轻颈动脉体完整大鼠的呼吸抑制,但不能减轻颈动脉体失神经大鼠的呼吸抑制。这些发现强调了芬太尼通过KORs激活颈动脉体传入,而不是通过µ阿片受体抑制脑干呼吸神经元,并表明KOR激动剂可能抵消阿片样物质对呼吸的中枢抑制作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.70
自引率
0.00%
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0
审稿时长
3 weeks
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