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.
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 (ΔIsc ) 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 ΔIsc in FSK- and VER-stimulated colonic tissue, respectively, in HA line. In the ileum, LOP increased ΔIsc in FSK- and VER-stimulated tissue and decreased ΔIsc 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.
['Wasilewski|A|A|', 'Misicka|A|A|', 'Sacharczuk|M|M|', 'Fichna|J|J|0000-0002-8443-4417']
D000701:Analgesics, Opioid D000818:Animals D002368:Castor Oil D003106:Colon D003967:Diarrhea D007082:Ileum D007413:Intestinal Mucosa D008139:Loperamide D008297:Male D051379:Mice D009270:Naloxone D009292:Narcotic Antagonists D013315:Stress, Psychological
endogenous opioid system irritable bowel syndrome ion transport secretory diarrhea