Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse.
Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse.
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发表时间：
1984-08
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通讯作者：
F. Porreca;H. Mosberg;R. Hurst;V. J. Hruby;Thomas F. Burks
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作者：
F. Porreca;H. Mosberg;R. Hurst;V. J. Hruby;Thomas F. Burks
在未麻醉的小鼠中研究了参与热镇痛（55℃热板）介导和脊髓和脊髓上水平胃肠转运抑制的阿片受体。评估了五种受体选择性化合物在两次静脉注射后引起镇痛和抑制转运的有效性。和鞘内给药；其中包括提议的 mu 激动剂，[D-Ala2，N-甲基-Phe4，Gly5-ol]脑啡肽 (DAGO)，提议的 delta 激动剂，[D-Pen2，L-Pen5]脑啡肽 (DPLPE)，[D-Pen2，D-Pen5]脑啡肽 (DPDPE)（构象受限的 delta 选择性脑啡肽类似物）和[D-Thr2、Thr6、Leu5]脑啡肽 (DTTLE) 和拟议的 κ 激动剂反式 3,4-二氯-N-甲基-N-[2-(1-吡咯烷基)-环己基]-苯乙酰胺甲磺酸盐 (U-50,488H)，以及非选择性 mu 作用激动剂吗啡。所有化合物均被发现在静脉注射后产生镇痛作用。行政; i.c.v 的效力排名顺序路线是DAGO大于DTTLE大于吗啡大于DPLPE大于DPDPE大于U-50,488H。大多数这些激动剂在静脉注射时的镇痛效果。明显的时间长达 40 分钟，只有 DTTLE 和 U-50,488H 的时间过程更短。类似地，所有化合物在鞘内给药后均产生镇痛反应，该途径的效力排序为DTTLE大于吗啡大于DAGO大于DPLPE大于DPDPE大于U-50,488H，并且所有化合物（U-50,488H除外）的作用持续时间长达20至40分钟。这些激动剂在鞘内给药后也抑制胃肠道转运，DAGO 的效力顺序大于 DTTLE 大于 DPLPE 大于吗啡 大于 DPDPE 大于 U-50,488H。（摘要截断为 250 字）
The opioid receptors involved in the mediation of thermal analgesia (55 degrees C hot-plate) and inhibition of gastrointestinal transit at the spinal and supraspinal levels were studied in unanesthetized mice. Five receptor-selective compounds were evaluated for effectiveness in eliciting analgesia and inhibiting transit after both i.c.v. and intrathecal administration; these included the proposed mu agonist, [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAGO), the proposed delta agonists, [D-Pen2, L-Pen5]enkephalin (DPLPE), [D-Pen2, D-Pen5]enkephalin (DPDPE) (conformationally constrained delta selective enkephalin analogs) and [D-Thr2, Thr6, Leu5]enkephalin (DTTLE), and the proposed kappa agonist, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate (U-50,488H), as well as the nonselective mu-acting agonist, morphine. All compounds were found to produce analgesia after i.c.v. administration; the rank order of potency by the i.c.v. route was DAGO greater than DTTLE greater than morphine greater than DPLPE greater than DPDPE greater than U-50,488H. The analgesic effectiveness of most of these agonists given i.c.v. was evident for up to 40 min, with only DTTLE and U-50,488H having briefer time courses. Similarly, all the compounds produced analgesic responses after intrathecal administration, with the rank order of potency by this route being DTTLE greater than morphine greater than DAGO greater than DPLPE greater than DPDPE greater than U-50,488H, and all compounds (except U-50,488H) had durations of action of up to 20 to 40 min. These agonists also inhibited gastrointestinal transit after intrathecal administration, with a rank order of potency of DAGO greater than DTTLE greater than DPLPE greater than morphine greater than DPDPE greater than U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)