Peripheral and central actions of orphanin FQ (nociceptin) on murine colon.
Peripheral and central actions of orphanin FQ (nociceptin) on murine colon.
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DOI：
10.1152/ajpgi.1999.276.1.g125
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
M. Osinski;Paul Bass;E. Gaumnitz
中科院分区：
文献类型：
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作者：
M. Osinski;Paul Bass;E. Gaumnitz
孤啡肽（Orphanin FQ，OFQ）又称孤啡肽（nociceptin），是一种新近发现的内源性肽，其结构类似于内源性阿片肽。本研究探讨了集中管理OFQ在体内小鼠胃肠和结肠运输的行动，以及OFQ的行动，对离体结肠。侧脑室注射孤啡肽剂量依赖性地抑制结肠推进活动。孤啡肽抑制结肠推进不受竞争性阿片受体拮抗剂纳洛酮的共同管理。当硫酸吗啡或δ-激动剂DPDPE与OFQ联合给药时，观察到亚加性反应。与μ-激动剂DAMGO联合给药时未观察到亚加性，表明OFQ和δ-阿片中枢通路之间存在调节结肠转运的功能性相互作用。高剂量（但非低剂量）的OFQ也抑制不可吸收的活性炭标记物通过胃和/或小肠的转运。OFQ有力地收缩离体结肠制备;收缩活性被TTX或氯丙嗪废除。我们的研究结果表明，OFQ可能是一个重要的肽配体作用于一个新的抑制性神经通路，调节胃肠运输。
Orphanin FQ (OFQ), also known as nociceptin, is a recently isolated endogenous peptide with a structure similar to the endogenous opioid peptides. The present study examines the actions of centrally administered OFQ on in vivo murine gastrointestinal and colonic transit as well as the actions of OFQ on the isolated colon. Intracerebroventricular injections of OFQ dose dependently inhibited colonic propulsive activity. OFQ inhibition of colonic propulsion was unaffected by coadministration of the competitive opioid receptor antagonist naltrexone. A subadditive response was observed when approximately equipotent doses of either morphine sulfate or the δ-agonist DPDPE were coadministered with OFQ. No subadditivity was observed with coadministration of the μ-agonist DAMGO, suggesting a functional interaction between OFQ and δ-opioid central pathways regulating colonic transit. High, but not low, doses of OFQ also inhibited the transit of a nonabsorbable charcoal marker through the stomach and/or small intestine. OFQ potently contracted isolated colon preparations; contractile activity was abolished by TTX or chlorpromazine. Our results suggest that OFQ may be an important peptide ligand acting on a novel inhibitory neural pathway that modulates gastrointestinal transit.