Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice.
Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice.
复制标题
一氧化二氮通过小鼠体内的 α2B 和/或 α2C 肾上腺素受体亚型产生抗伤害反应。
作者：
T. Guo;M. Davies;W. Kingery;A. Patterson;L. Limbird;M. Maze
背景
大鼠中脑导水管周围灰质区的阿片受体和脊髓中的α 2肾上腺素受体介导了一氧化二氮（N2O）的抗伤害感受特性。基因改变小鼠的可用性有助于检测转导途径中涉及的精确蛋白质种类。在这项研究中，作者建立了大鼠和小鼠之间的相似性，在抗伤害作用的N2O和调查α 2肾上腺素受体亚型介导这种反应。
方法
在获得机构批准后，在野生型和转基因小鼠（D79N）中测量了对N2O的抗伤害性剂量反应和时程，使用甩尾潜伏期测定了非功能性α 2A肾上腺素受体。用育亨宾（非选择性α_2受体拮抗剂）、纳洛酮（阿片受体拮抗剂）、L659、066（外周α_2受体拮抗剂）和哌唑嗪（α_2B和α_2C受体选择性拮抗剂）全身预处理后，观察N_2O的镇痛作用。在野生型和转基因小鼠中测试了对右旋美托咪啶（D-med）（一种非选择性α 2激动剂）的甩尾潜伏期。
结果
N2O在D79N转基因小鼠和野生型同窝小鼠中均产生抗伤害感受作用，但在转基因小鼠中的反应不太明显。随着时间的推移，持续暴露N2O的抗伤害感受降低，并且在转基因小鼠中的递减更为明显。阿片受体和选择性α 2B-/α 2C-受体拮抗剂可以剂量依赖性地拮抗抗伤害性反应，但中枢神经系统不渗透性α 2拮抗剂不能拮抗（L659，066）。尽管右旋美托咪定在D79N小鼠中未表现出抗伤害感受性应答，但野生型同窝小鼠中的强抗伤害感受性应答不能被选择性α 2B-/α 2C-受体拮抗剂阻断。
结论
这些数据证实，对外源性α 2-激动剂的抗伤害性反应是由α 2A肾上腺素受体介导的，并且在对N2O的镇痛反应中，α 2B-或α 2C-肾上腺素受体亚型或两者似乎都有作用。
BACKGROUND
Opiate receptors in the periaqueductal gray region and alpha2 adrenoceptors in the spinal cord of the rat mediate the antinociceptive properties of nitrous oxide (N2O). The availability of genetically altered mice facilitates the detection of the precise protein species involved in the transduction pathway. In this study, the authors establish the similarity between rats and mice in the antinociceptive action of N2O and investigate which alpha2 adrenoceptor subtypes mediate this response.
METHODS
After obtaining institutional approval, antinociceptive dose-response and time-course to N2O was measured in wild-type and transgenic mice (D79N), with a nonfunctional alpha2A adrenoceptor using tail-flick latency. The antinociceptive effect of N2O was tested after pretreatment systemically with yohimbine (nonselective alpha2 antagonist), naloxone (opiate antagonist), L659,066 (peripheral alpha2-antagonist) and prazosin (alpha2B- and alpha2C-selective antagonist). The tail-flick latency to dexmedetomidine (D-med), a nonselective alpha2 agonist, was tested in wild-type and transgenic mice.
RESULTS
N2O produced antinociception in both D79N transgenic and wild-type litter mates, although the response was less pronounced in the transgenic mice. Antinociception from N2O decreased over time with continuing exposure, and the decrement was more pronounced in the transgenic mice. The antinociceptive response could be dose dependently antagonized by opiate receptor and selective alpha2B-/alpha2C-receptor antagonists but not by a central nervous system-impermeant alpha2 antagonist (L659,066). Whereas dexmedetomidine exhibited no antinociceptive response in the D79N mice, the robust antinociceptive response in the wild-type litter mates could not be blocked by a selective alpha2B-/alpha2C-receptor antagonist.
CONCLUSION
These data confirm that the antinociceptive response to an exogenous alpha2-agonist is mediated by an alpha2A adrenoceptor and that there appears to be a role for the alpha2B- or alpha2C-adrenoceptor subtypes, or both, in the analgesic response to N2O.
人脑中 α-2 肾上腺素受体亚型的表征。
DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ordway,GA;Jaconetta,SM;Halaris,AE
通讯作者：
Halaris,AE
通过位点特异性 mu 和 epsilon 阿片受体阻断，在大鼠热板试验中拮抗一氧化二氮镇痛作用。
DOI：
--
发表时间：
1994
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Hodges,BL;Gagnon,MJ;Gillespie,TR;Breneisen,JR;O'Leary,DF;Hara,S;Quock,RM
通讯作者：
Quock,RM
DOI：
10.1073/pnas.94.18.9950
发表时间：
1997-09-02
影响因子：
11.1
作者：
Lakhlani, PP;MacMillan, LB;Limbird, LE
通讯作者：
Limbird, LE