Nociceptin effect on intestinal motility depends on opioidreceptor like-1 receptors and nitric oxide synthase colocalization

• 作者: Andrei Sibaev Birol Yuece Dieter Saur Jakub Fichna Jean-Pierre Timmermans Martin Storr
• 来源期刊: 世界胃肠药理与治疗学杂志：英文版（电子版）
• 学科: 医学
• 关键词: NOCICEPTIN Gastrointestinal TRANSIT Opioidreceptor like-1 ELECTROPHYSIOLOGY Expression
• 年，卷（期）: sjwcylyzlxzzywbdzb_2015,（3）
• 页码范围: 73-83
• 页数: 11页
• 分类号: R57

摘要

AIM: To study the effect of the opioid-receptor like-1(ORL1) agonist nociceptin on gastrointestinal(GI)myenteric neurotransmission and motility. METHODS: Reverse transcriptase- polymerase chain reaction and immunohistochemistry were used to localize nociceptin and ORL1 in mouse tissues. Intracellular electrophysiological recordings of excitatory and inhibitory junction potentials(EJP, IJP) were made in a chambered organ bath. Intestinal motility was measured in vivo. RESULTS: Nociceptin accelerated whole and upper GI transit, but slowed colonic expulsion in vivo in an ORL1-dependent manner, as shown using [Nphe1]NOC and AS ODN pretreatment. ORL1 and nociceptin immunoreactivity were found on enteric neurons. Nociceptin reduced the EJP and the nitric oxide-sensitive slow IJP in an ORL1-dependent manner, whereas the fast IJP was unchanged. Nociceptin further reduced the spatial spreading of the EJP up to 2 cm. CONCLUSION: Compounds acting at ORL1 are good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome.