κ-阿片受体急性激活后豚鼠离体回肠的戒断挛缩

Withdrawal contractures of guinea-pig isolated ileum after acute activation of kappa-opioid receptors.

作者信息

Morrone L A, Romanelli L, Amico M C, Valeri P

机构信息

Institute of Pharmacology and Pharmacognosy, University of Rome La Sapienza, Italy.

出版信息

Br J Pharmacol. 1993 May;109(1):48-52. doi: 10.1111/j.1476-5381.1993.tb13529.x.

DOI:10.1111/j.1476-5381.1993.tb13529.x

PMID:8388301

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175595/

Abstract

The present study was undertaken to investigate firstly whether a brief exposure for 5 min of guinea-pig isolated ileum to the kappa-opioid agonist, U-50,488H produced a withdrawal contracture on addition of naloxone and secondly to ascertain whether the response was due to the activation of kappa-opioid receptors. 2. Naloxone (10(-6) M) did not elicit a response in preparations exposed to U-50,488H (5 x 10(-7) M-2 x 10(-6) M). However, after exposure to U-50,488H (5 x 10(-7) M), naloxone (10(-6) M) produced a strong contracture if the agonist was washed out 1 min before the addition of the antagonist. 3. The addition of naloxone (10(-6) M) to the ileum preparation exposed to U-50,488H (10(-7) M or lower) caused a response of similar intensity irrespective of whether the agonist had been washed out. 4. The selective kappa-opioid antagonist, nor-binaltorphimine (2.7 x 10(-9) M and 2.7 x 10(-7) M), injected before the opioid agonists, prevented the naloxone-induced contracture after exposure to U-50,488H (8 x 10(-8) M) but did not affect the contracture after exposure to morphine (5 x 10(-7) M). 5. Nor-binaltorphimine (2.7 x 10(-9) M) caused a contraction of the ileum preparation when injected 5 min after exposure to U-50,488H (8 x 10(-8) M) but not after morphine (5 x 10(-7) M). 6. The alpha 2-adrenoceptor agonist, clonidine (3 x 10-8 M) and the calcium channel blocker, nifedipine(3 x 10-8 M), injected 1 min before naloxone, blocked the ileum contraction to naloxone after exposure to U-50,488H (8 x 10-8 M). The results demonstrate that the stimulation of Kappa-opioid receptors can induce a similar dependence in guinea-pig ileum to that produced by activation of micro receptors.

摘要

本研究旨在首先探究豚鼠离体回肠短暂暴露于κ-阿片受体激动剂U-50,488H 5分钟后，加入纳洛酮是否会产生戒断性挛缩，其次确定该反应是否归因于κ-阿片受体的激活。2. 纳洛酮（10⁻⁶ M）在暴露于U-50,488H（5×10⁻⁷ M - 2×10⁻⁶ M）的制剂中未引发反应。然而，在暴露于U-50,488H（5×10⁻⁷ M）后，如果在加入拮抗剂前1分钟将激动剂洗脱，纳洛酮（10⁻⁶ M）会产生强烈的挛缩。3. 无论激动剂是否已被洗脱，向暴露于U-50,488H（10⁻⁷ M或更低浓度）的回肠制剂中加入纳洛酮（10⁻⁶ M）都会引起强度相似的反应。4. 在给予阿片类激动剂之前注射选择性κ-阿片受体拮抗剂诺宾那托啡（2.7×10⁻⁹ M和2.7×10⁻⁷ M），可预防暴露于U-50,488H（8×10⁻⁸ M）后纳洛酮诱导的挛缩，但不影响暴露于吗啡（5×10⁻⁷ M）后的挛缩。5. 在暴露于U-50,488H（8×10⁻⁸ M）后5分钟注射诺宾那托啡（2.7×10⁻⁹ M）会引起回肠制剂收缩，但在暴露于吗啡（5×10⁻⁷ M）后则不会。6. 在纳洛酮前1分钟注射α₂-肾上腺素能受体激动剂可乐定（3×10⁻⁸ M）和钙通道阻滞剂硝苯地平（3×10⁻⁸ M），可阻断暴露于U-50,488H（8×10⁻⁸ M）后回肠对纳洛酮的收缩反应。结果表明，κ-阿片受体的刺激可在豚鼠回肠中诱导出与μ受体激活所产生的类似依赖性。