Nishiwaki H, Saitoh N, Nishio H, Takeuchi T, Hata F
Department of Veterinary Pharmacology, College of Agriculture, Osaka Prefecture University, Sakai, Japan.
Jpn J Pharmacol. 1998 Aug;77(4):279-86. doi: 10.1254/jjp.77.279.
Relationship between activation of opioid receptors and muscarinic autoinhibition in acetylcholine (ACh) release from the myenteric plexus was studied in longitudinal muscle myenteric plexus (LMMP) preparations of guinea pig ileum. A mu-receptor agonist, [D-Ala2, N-Me-Phe4, Gly5-ol] enkephalin (DAMGO), at a concentration of 1 microM inhibited the ACh release evoked by electrical field stimulation (EFS) at 1 Hz but not at 10 Hz. After the muscarinic autoreceptors were blocked with atropine (1 microM), DAMGO inhibited EFS-evoked ACh release also at 10 Hz. After the autoreceptors were potently activated with muscarine (200 microM), the inhibitory effect of DAMGO at 1 Hz was abolished. A kappa-receptor agonist, U-50,488, at 1 microM inhibited the EFS-evoked ACh release both at 1 and 10 Hz. U-50,488 inhibited ACh release regardless of the presence of atropine or muscarine. A delta-agonist, enkephalin [D-PEN2.5] (PDPDE), did not show any significant effect. On the other hand, a selective mu-receptor antagonist, cyprodime, increased ACh release evoked by EFS at 1 Hz, but not at 10 Hz. After the autoreceptors were blocked, cyprodime increased EFS-evoked ACh release also at 10 Hz. The selective kappa-receptor antagonist, nor-binaltorphimine, did not affect ACh release in the absence or presence of atropine. The results suggest that endogenous opioid(s) inhibits ACh release by activating mu-, but not kappa- and delta-receptors in the LMMP of guinea pig ileum and that the inhibitory effect of endogenous opioid(s) in the ACh release is important when muscarinic autoinhibition mechanism does not fully work.
在豚鼠回肠的纵行肌肌间神经丛（LMMP）制备物中，研究了阿片受体激活与毒蕈碱对肌间神经丛乙酰胆碱（ACh）释放的自身抑制之间的关系。μ受体激动剂[D - Ala2，N - Me - Phe4，Gly5 - ol]脑啡肽（DAMGO），浓度为1μM时可抑制1Hz电场刺激（EFS）诱发的ACh释放，但对10Hz的EFS诱发的ACh释放无抑制作用。在用阿托品（1μM）阻断毒蕈碱自身受体后，DAMGO对10Hz的EFS诱发的ACh释放也有抑制作用。在用毒蕈碱（200μM）强力激活自身受体后，DAMGO在1Hz时的抑制作用消失。κ受体激动剂U - 50,488，浓度为1μM时，对1Hz和10Hz的EFS诱发的ACh释放均有抑制作用。无论有无阿托品或毒蕈碱，U - 50,488均能抑制ACh释放。δ激动剂脑啡肽[D - PEN2.5]（PDPDE）未显示出任何显著作用。另一方面，选择性μ受体拮抗剂环丙二甲基吗啡，可增加1Hz EFS诱发的ACh释放，但对10Hz的EFS诱发的ACh释放无此作用。在阻断自身受体后，环丙二甲基吗啡对10Hz的EFS诱发的ACh释放也有增加作用。选择性κ受体拮抗剂去甲二氢吗啡酮，无论有无阿托品，均不影响ACh释放。结果表明，内源性阿片类物质通过激活豚鼠回肠LMMP中的μ受体而非κ和δ受体来抑制ACh释放，并且当毒蕈碱自身抑制机制不能充分发挥作用时，内源性阿片类物质对ACh释放的抑制作用很重要。
