NITROUS-OXIDE SELECTIVELY RELEASES MET(5)-ENKEPHALIN AND MET(5)-ENKEPHALIN-ARG(6)-PHE(7) INTO CANINE 3RD VENTRICULAR CEREBROSPINAL-FLUID
NITROUS-OXIDE SELECTIVELY RELEASES MET(5)-ENKEPHALIN AND MET(5)-ENKEPHALIN-ARG(6)-PHE(7) INTO CANINE 3RD VENTRICULAR CEREBROSPINAL-FLUID
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DOI：
10.1097/00000539-199504000-00003
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发表时间：
1995-04-01
影响因子：
5.7
通讯作者：
NGAI, SH
中科院分区：
文献类型：
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作者：
FINCK, AD;SAMANIEGO, E;NGAI, SH
阿片受体-内源性阿片肽系统在氧化亚氮镇痛中的作用机制一直是一个有争议的问题。大多数先前的研究仅提供间接证据来支持或反驳阿片受体和/或内源性阿片肽的参与。为了提供更直接的证据，我们测量了五个自然发生的内源性阿片肽的浓度在第三脑室脑脊液从8个驯化的狗长期植入脑室导管。当通过面罩呼吸室内空气或66-75体积%的一氧化二氮氧气时，从每只动物中获得成对的脑脊液样本。使用反相高效液相色谱法对内源性阿片肽进行物理分离，并使用放射免疫测定法进行定量。吸入一氧化二氮使脑脊液中甲硫氨酸脑啡肽浓度从对照值0.30 +/- 0.07（平均值+/- SEM，n = 8）增加到42.4 +/- 8.1 pmol/mL（P = 0.0006）。增加幅度从对照值的28倍到400倍以上不等。甲硫氨酸（5）-脑啡肽-精氨酸（6）-苯丙氨酸（7）浓度也从14.5 +/- 2.5增加到57.6 +/- 17.8 pmol/mL（P = 0.018）。强啡肽A、强啡肽B或β-内啡肽的浓度未观察到显著变化。这些结果直接支持了一氧化氮诱导的镇痛作用涉及脑啡肽原衍生的内源性阿片肽家族的假设。
The rule of the opioid receptor-endogenous opioid peptide system in mediating analgesia induced by nitrous oxide has been a controversial subject. Most previous studies provided only indirect evidence either to support or refute the involvement of opioid receptors and/or endogenous opioid peptides. To provide more direct evidence, we measured concentrations of five naturally occurring endogenous opioid peptides in third ventricular cerebrospinal fluid from eight acclimated dogs with chronically implanted ventricular catheters. Paired samples of cerebrospinal fluid were obtained from each animal when breathing room air or 66-75 vol% nitrous oxide in oxygen through a face mask. Endogenous opioid peptides were physically separated using reversed phase high-performance liquid chromatography and quantified using radioimmunoassays. Nitrous oxide inhalation increased cerebrospinal fluid concentrations of met(5)-enkephalin from a control value of 0.30 +/- 0.07 (mean +/- SEM, n = 8) to 42.4 +/- 8.1 pmol/mL (P = 0.0006). Increases ranged from 28 to more than 400 times the control value. Met(5)-enkephalin-arg(6)-phe(7) concentrations also increased from 14.5 +/- 2.5 to 57.6 +/- 17.8 pmol/mL (P = 0.018). No significant changes were noted in concentrations of dynorphin A, dynorphin B, or beta-endorphin. These results directly support the hypothesis that nitrous-oxide-induced analgesia involves the proenkephalin-derived family of endogenous opioid peptides.