脑桥柯利克 - 富斯神经元上μ阿片受体的脱敏和耐受
Desensitization and Tolerance of Mu Opioid Receptors on Pontine Kölliker-Fuse Neurons.
作者信息
Levitt Erica S, Williams John T
机构信息
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida (E.S.L.) and Vollum Institute, Oregon Health and Science University, Portland, Oregon (J.T.W.)
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida (E.S.L.) and Vollum Institute, Oregon Health and Science University, Portland, Oregon (J.T.W.).
出版信息
Mol Pharmacol. 2018 Jan;93(1):8-13. doi: 10.1124/mol.117.109603. Epub 2017 Nov 2.
Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein-coupled inwardly rectifying potassium current was measured using whole-cell voltage-clamp recordings from KF and locus coeruleus (LC) neurons contained in acute rat brain slices. A saturating concentration of the opioid agonist [Met]-enkephalin (ME) caused significantly less desensitization in KF neurons compared with LC neurons. In contrast to LC, desensitization in KF neurons was not enhanced by activation of protein kinase C or in slices from morphine-treated rats. Cellular tolerance to ME and morphine was also lacking in KF neurons from morphine-treated rats. The lack of cellular tolerance in KF neurons correlates with the relative lack of tolerance to the respiratory depressant effect of opioids.
μ阿片受体的急性脱敏被认为是对阿片类药物产生耐受性的初始步骤。鉴于呼吸系统对产生耐受性具有抗性，因此对呼吸回路中的关键区域柯利克-福斯（KF）神经元的脱敏进行了研究。使用急性大鼠脑片所含KF和蓝斑（LC）神经元的全细胞膜片钳记录来测量G蛋白偶联内向整流钾电流的激活。与LC神经元相比，阿片类激动剂[Met]-脑啡肽（ME）的饱和浓度在KF神经元中引起的脱敏明显较少。与LC不同，蛋白激酶C的激活或吗啡处理大鼠的脑片并未增强KF神经元的脱敏。吗啡处理大鼠的KF神经元对ME和吗啡也缺乏细胞耐受性。KF神经元中缺乏细胞耐受性与对阿片类药物呼吸抑制作用相对缺乏耐受性相关。
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