Tachykinin antagonists ameliorate surgically induced impairment of gastrointestinal motility in rats

• Published in: Fundamental & clinical pharmacology 2021-08, Vol.35 (4), p.681-689
• Main Authors: Umer, Artur, Ługowska‐Umer, Hanna, Schönborn‐Kellenberger, Oliver, Korolkiewicz, Paweł K., Sein‐Anand, Łukasz, Kocic, Ivan, Korolkiewicz, Roman P.
• Format: Article
• Language: English
• Subjects: Anesthesia; Animals; Carbachol - pharmacology; Diethyl ether; Digestive system; Disease Models, Animal; Gastric motility; Gastrointestinal Motility - drug effects; Gastrointestinal tract; Ileus - prevention & control; Laparotomy; Motility; nolpitantium; Pharmacology; Postoperative Complications - prevention & control; postoperative ileus; Pretreatment; Random Allocation; Rats; Rats, Wistar; Reagents; Receptors; Receptors, Tachykinin - antagonists & inhibitors; Rodents; saredutant; SB222200; Skin; Small intestine; Surgery; Tachykinin; Tachykinin receptors; tachykinins; Transit
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12616

The protective effects of tachykinin receptor antagonists: SR140333 (NK1 receptor), SR48968 (NK2 receptor), and SB222200 (NK3 receptor) were tested in rats against a surgically induced postoperative inhibition of gut motility, a common complication of abdominal surgery. The small intestinal transit of Evans blue was measured 24‐h post‐surgery in untreated rats and animals subjected to skin incision, laparotomy, or laparotomy followed by gut evisceration and manipulation. Surgical procedures were conducted under diethyl ether anesthesia. In comparison to untreated and ether‐anesthetized rats, animals undergoing skin incision, laparotomy, or laparotomy with gut evisceration and manipulation showed a significant decrease in the intestinal transit of Evans blue. The pretreatment with NK1 (3–100 µg/kg), NK2 (3–30 µg/kg), and NK3 (10–300 µg/kg) blockers before surgery ameliorated the inhibitory effects of gut manipulation in a dose‐dependent manner. Moreover, the submaximal and maximal doses of NK3 antagonists showed a trend toward reversing not only the inhibition caused by gut manipulation but also laparotomy. An additive effect of combining submaximal doses of NK1‐3 blockers was observed in animals pretreated with NK1 + NK2 compared to single‐agent NK1 and NK2. Additionally, doublets: NK1 + NK3 or NK2 + NK3 and a triplet: NK1 + NK2 + NK3 proved to be more effective than NK2 antagonist alone. In contrast, NK1‐3 blockers have not markedly affected the intestinal propulsion in untreated rats or animals subjected to skin incision or laparotomy. NK1‐3 blockers ameliorated the suppressed small‐bowel gut motility 24 post‐surgery. Combined pretreatment with NK1‐3 antagonists provided selective, additive benefits compared to single agents.