Prosecretory effect of loperamide in ileal and colonic mucosae of mice displaying high or low swim stress‐induced analgesia associated with high and low endogenous opioid system activity. Issue 2 (26th July 2017)

• Record Type: Journal Article
• Authors: Wasilewski, A.; Misicka, A.; Sacharczuk, M.; Fichna, J.
• Is Part Of: Neurogastroenterology & motility. Volume 30:Issue 2(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-07-26
• Subjects: endogenous opioid system -- ion transport -- irritable bowel syndrome -- secretory diarrhea; Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.13166
• Languages: English
• ISSNs: 1350-1925

Abstract

Abstract: Background: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and changes in bowel habit. The aim of this study was to characterize the effect of loperamide hydrochloride (LOP) and naloxone hydrochloride (NLX), an opioid agonist and antagonist, respectively, on electrolyte equilibrium in ileal and colonic mucosae and to estimate the possible influence of divergent activity of the endogenous opioid system (EOS) on IBS therapy. Methods: Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress‐induced analgesia associated with high and low EOS activity were used in this study. To assess the effect of LOP and NLX on HA/LA lines in vivo, we used the castor oil‐induced diarrhea model. Changes in electrolyte equilibrium were determined on the basis of short‐circuit current (Δ I sc ) in isolated mouse ileum and colon exposed to LOP and NLX and stimulated by forskolin (FSK), veratridine (VER), and bethanechol (BET). Key Results: In vivo, we found that LOP significantly prolonged time to appearance of diarrhea in HA and LA lines. In vitro, LOP and NLX increased Δ I sc in FSK‐ and VER‐stimulated colonic tissue, respectively, in HA line. In the ileum, LOP increased Δ I sc in FSK‐ and VER‐stimulated tissue and decreased Δ I sc in BET‐stimulated tissues in HA line. Conclusions & Inferences: Individual differences in EOS activity may play a crucial role in the response to the IBS‐D therapy, thus some patients may be at an increased risk of side effects such as constipation or diarrhea. Abstract : Our study shows that increased or decreased activity of the endogenous opioid system in each individual may cause the side effects during prolonged, antidiarrheal therapy with loperamide and other opioids. These findings may be crucial for development of novel effective opioid agents devoid of gastrointestinal side effects during IBS‐D treatment.