Taniguchi H, Yomota E, Nogi K, Onoda Y, Ikezawa K
Discovery Research Laboratory, Tanabe Seiyaku, Toda, Saitama, Japan.
Eur J Pharmacol. 1998 Jul 24;353(2-3):265-71. doi: 10.1016/s0014-2999(98)00411-7.
To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.
为评估类阿片受体样1（ORL1）受体在肠道运动中的作用，我们研究了孤啡肽对大鼠结肠收缩和转运的影响。孤啡肽（0.1 - 100 nM）可浓度依赖性地引起离体结肠立即出现强直性收缩，随后出现节律性收缩波。孤啡肽（10 nM）引起的反应不受经典阿片受体拮抗剂纳洛酮、纳曲吲哚和去甲双氢吗啡酮的影响。使用垂体腺苷酸环化酶激活多肽（6 - 38）（PACAP -（6 - 38）；3 μM）、血管活性肠肽（10 - 28）（VIP -（10 - 28）；3 μM）和N（ω）-硝基-L-精氨酸甲酯（L-NAME；100 μM）抑制抑制性神经递质的作用，并不影响孤啡肽诱导的收缩。在麻醉大鼠中，静脉注射孤啡肽（1 μg/kg）或吗啡（1 mg/kg）可引起近端结肠的阶段性收缩。纳洛酮（300 μg/kg，静脉注射）预处理可消除吗啡诱导的收缩，但不能消除孤啡肽诱导的收缩。孤啡肽（0.03 - 3 μg/kg，皮下注射）可剂量依赖性地加速大肠转运，但吗啡（1.7 - 5 mg/kg，皮下注射）则使其减慢。这些结果表明，刺激ORL1受体可独立于阿片受体加速结肠收缩和转运。
