Ozaki M, Miyamoto Y, Kishioka S, Masuda Y, Yamamoto H
Department of Toxicology, Niigata College of Pharmacy, Japan.
Neuropharmacology. 1994 May;33(5):671-9. doi: 10.1016/0028-3908(94)90173-2.
The participation of opioid receptor types in the inhibition of the twitch (0.1 Hz, 0.5 msec duration, maximum intensity) following high frequency stimulation (10 Hz, 0.5 msec duration, maximum intensity for 1 min) (post-tetanic twitch inhibition) was investigated in isolated guinea-pig ileal longitudinal muscle using highly selective mu, kappa and delta opioid receptor antagonists. The mu antagonist, beta-funaltrexamine (beta-FNA), produced a concentration-dependent twitch inhibition, which disappeared with thorough washing. The concentration-response curve of the twitch inhibition for morphine was shifted rightward about 10-20-fold by beta-FNA pre-exposure, whereas that for dynorphin 1-13 inhibition remained unchanged. However, after thorough washing of beta-FNA the twitch inhibition of morphine continued during the post-tetanic twitch inhibition for as long as it was tested. The post-tetanic twitch inhibition was partially antagonized by beta-FNA pretreatment and further antagonized by additional exposure to naloxone (NLX). In the presence of nor-binaltorphimine (nor-BNI), a kappa antagonist, which has no effect on the twitch inhibition of morphine, the concentration-response curve of the twitch inhibition of dynorphin 1-13 was shifted rightward approx 100-fold. The post-tetanic twitch inhibition was antagonized by nor-BNI, and no further antagonism was produced by NLX. (Allyl)2-Tyr-Aib-Aib-Phe-Leu (ICI 174,864), a delta antagonist, did not affect the post-tetanic twitch inhibition. These results suggest that both mu and kappa opioid receptors participate in post-tetanic twitch inhibition in isolated guinea-pig ileal myenteric plexus-longitudinal muscle (MPLM).
利用高选择性的μ、κ和δ阿片受体拮抗剂，在离体豚鼠回肠纵行肌中研究了阿片受体类型在高频刺激（10Hz，持续时间0.5毫秒，最大强度，持续1分钟）后对抽搐（0.1Hz，持续时间0.5毫秒，最大强度）的抑制作用（强直后抽搐抑制）。μ拮抗剂β-芬太尼酰苯胺（β-FNA）产生浓度依赖性的抽搐抑制作用，彻底冲洗后该作用消失。预先暴露于β-FNA可使吗啡引起的抽搐抑制浓度-反应曲线右移约10至20倍，而强啡肽1-13抑制的浓度-反应曲线保持不变。然而，彻底冲洗β-FNA后，只要进行测试，吗啡引起的抽搐抑制在强直后抽搐抑制期间会持续存在。β-FNA预处理可部分拮抗强直后抽搐抑制，额外暴露于纳洛酮（NLX）可进一步拮抗。在κ拮抗剂去甲二氢吗啡酮（nor-BNI）存在下，其对吗啡引起的抽搐抑制无影响，强啡肽1-13引起的抽搐抑制浓度-反应曲线右移约100倍。强直后抽搐抑制可被nor-BNI拮抗，NLX不会产生进一步的拮抗作用。δ拮抗剂（烯丙基）2-酪氨酸-丙氨酸-丙氨酸-苯丙氨酸-亮氨酸（ICI 174,864）不影响强直后抽搐抑制。这些结果表明，μ和κ阿片受体均参与离体豚鼠回肠肌间神经丛-纵行肌（MPLM）的强直后抽搐抑制。
