Suh H H, Tseng L F
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
J Pharmacol Exp Ther. 1990 Jun;253(3):981-6.
The present studies were designed to determine what type of opioid receptor, mu or delta, in the spinal cord was involved in beta-endorphin-induced antinociception. The tail-flick response was used as an antinociceptive test. Intrathecal (i.t.) injection of ICI-174,864 [(Allyl)2-Tyr-Aib-Aib-Phe-Leu-OH] (10 micrograms) or ICI-154,129 [(N,N-Bisallyl)-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH] (20 micrograms), delta-opioid receptor antagonists, but not beta-funaltrexamine (0.025 microgram), a mu-opioid receptor antagonist, antagonized inhibition of the tail-flick response induced by beta-endorphin given i.c.v. However, i.t. injection of the same dose of ICI-174,864, ICI-154,129 or beta-funaltrexamine did not affect inhibition of the tail-flick response induced by morphine given i.c.v. Mice were pretreated i.c.v. with either beta-endorphin (2 micrograms), morphine (2 micrograms) or saline (5 microliters) for 2, 3 or 4 hr (which were times that the tail-flick response was no longer inhibited) and were injected i.t. with various doses of D-Ala2-NMePhe4-Gly-ol-enkephalin (a selective mu-opioid receptor agonist), D-Ala2-D-Leu5-enkephalin (a mu- and delta-opioid receptor agonist) or D-Pen2-D-Pen5-enkephalin (a delta-opioid receptor agonists). The tail-flick response was performed 10 min after i.t. injection. A single i.c.v. pretreatment with beta-endorphin for 2 and 3 hr, but not 4 hr, reduced markedly the inhibition of the tail-flick response induced by D-Pen2-D-Pen5-enkephalin and D-Ala2-DLeu5-enkephalin, but not D-Ala2-NMePhe4-Gly-ol-enkephalin, injected i.t.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在确定脊髓中何种类型的阿片受体(μ受体或δ受体)参与β-内啡肽诱导的镇痛作用。甩尾反应用作镇痛测试。鞘内注射ICI-174,864 [(烯丙基)2-酪氨酸-丙氨酸-丙氨酸-苯丙氨酸-亮氨酸-OH](10微克)或ICI-154,129 [(N,N-双烯丙基)-酪氨酸-甘氨酸-甘氨酸-ψ-(CH2S)-苯丙氨酸-亮氨酸-OH](20微克),δ阿片受体拮抗剂,但不是μ阿片受体拮抗剂β-氟纳曲明(0.025微克),可拮抗脑室内给予β-内啡肽诱导的甩尾反应抑制。然而,鞘内注射相同剂量的ICI-174,864、ICI-154,129或β-氟纳曲明并不影响脑室内给予吗啡诱导的甩尾反应抑制。给小鼠脑室内预先注射β-内啡肽(2微克)、吗啡(2微克)或生理盐水(5微升)2、3或4小时(这些时间点甩尾反应不再受抑制),然后鞘内注射不同剂量的D-Ala2-NMePhe4-Gly-ol-脑啡肽(一种选择性μ阿片受体激动剂)、D-Ala2-D-Leu5-脑啡肽(一种μ和δ阿片受体激动剂)或D-Pen2-D-Pen5-脑啡肽(一种δ阿片受体激动剂)。鞘内注射10分钟后进行甩尾反应测试。脑室内单次预先注射β-内啡肽2小时和3小时,但不是4小时,可显著降低鞘内注射D-Pen2-D-Pen5-脑啡肽和D-Ala2-DLeu5-脑啡肽诱导的甩尾反应抑制,但不影响鞘内注射D-Ala2-NMePhe4-Gly-ol-脑啡肽诱导的甩尾反应抑制。(摘要截短于250字)