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The antinociceptive action of P-317 was characterized in the mustard oil-induced abdominal pain model and the writhing test. Locomotor activity and grip-strength tests were used to evaluate the effect of P-317 in the central nervous system (CNS). To translate our study to clinical conditions, the semi-quantitative expression of \u03bc-opioid receptors (MOP) and \u03ba-opioid receptors (KOP) messenger RNA (mRNA) in human colonic samples from IBS-D patients was quantified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key findings<\/jats:title><jats:p>In vitro, P-317 (10\u221210\u201310\u22126 M) inhibited colonic and ileal smooth muscle contractions in a concentration-dependent, \u03b2-funaltrexamine and nor-binaltorphimine-reversible manner. In vivo, P-317 (0.1 mg\/kg, i.p. and 1 mg\/kg, p.o.) inhibited GI transit, displayed a potent antinociceptive action in abdominal pain tests and did not influence the CNS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>P-317 produced a potent analgesic and antidiarrhoeal action in the mouse GI tract after oral administration. Given lower expression of MOP and KOP mRNA in IBS-D patients, P-317 is a promising peptide-based drug candidate for IBS-D therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jphp.12335","type":"journal-article","created":{"date-parts":[[2014,12,17]],"date-time":"2014-12-17T06:51:12Z","timestamp":1418799072000},"page":"244-254","source":"Crossref","is-referenced-by-count":21,"title":["Orally administered novel cyclic pentapeptide P-317 alleviates symptoms of diarrhoea-predominant irritable bowel syndrome"],"prefix":"10.1093","volume":"67","author":[{"given":"Marta","family":"Zieli\u0144ska","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Medical University of Lodz , Lodz,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Tenth People\u2019s Hospital of Shanghai, School of Medicine, Tongji University 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