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Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats.
J Surg Res. 2020 Jul 03; 255:510-516.JS

Abstract

BACKGROUND

Supraceliac aortic clamping and unclamping produces ischemia-reperfusion (I/R) injury of the splanchnic organs. The protective effects of tachykinin receptor antagonists, SR140333 (NK1 receptor), SR48968 (NK2 receptor), and SB222200 (NK3 receptor), against I/R-induced inhibition of intestinal motility were tested in rats.

MATERIAL AND METHODS

The intestinal transit of Evans blue was measured in untreated rats and animals subjected to skin incision, I/R (1 h superior mesenteric artery occlusion followed by 24 h reperfusion) or sham operation. Surgical procedures were conducted under diethyl ether anesthesia.

RESULTS

The gastrointestinal transit has not been markedly affected in rats, which were anesthetized or subjected to skin incision in comparison with untreated animals. In contrast, a sham operation and I/R have significantly reduced the intestinal motility. Pretreatment with NK1-3 blockers (SR140333 [3-30 μg/kg]; SR48968 [3-100 μg/kg]; and SB222200 [10-100 μg/kg]) reversed dose dependently the effects of I/R to the level observed after sham operation only. A combination of NK1+NK2+NK3 inhibitors exerted an additive effect compared with NK1 and NK2 antagonists used as single agents. Similarly, combined NK1+NK2 were more effective than NK2 alone. Sham operation and I/R have shifted the in vitro carbachol concentration-response curves to the right in comparison with untreated animals, a phenomenon partially reversed by NK1-NK3 pretreatment.

CONCLUSIONS

Single-agent and combined treatment with NK1-3 antagonists markedly attenuated the gastrointestinal dysmotility evoked by I/R injury. The pretreatment with NK3 blocker proved to be the most active in this experimental setting.

Authors+Show Affiliations

Department of Thoracic Surgery, Medical University of Gdansk, Smoluchowskiego, Gdańsk, Poland.Department of Dermatology, Venerology, Allergology, Medical University of Gdańsk, Gdańsk, Poland.Cogitars GmbH, Heidelberg, Germany.Medical University of Gdańsk, Gdańsk, Poland.Department of Clinical Toxicology, Medical University of Gdańsk, Gdańsk, Poland.Department of Allergology and Pneumonology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.Department of Pharmacology, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: romankorolkiewicz@yahoo.co.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32629333

Citation

Umer, Artur, et al. "Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats." The Journal of Surgical Research, vol. 255, 2020, pp. 510-516.
Umer A, Ługowska-Umer H, Schönborn-Kellenberger O, et al. Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats. J Surg Res. 2020;255:510-516.
Umer, A., Ługowska-Umer, H., Schönborn-Kellenberger, O., Korolkiewicz, P. K., Sein-Anand, Ł., Kuziemski, K., & Korolkiewicz, R. P. (2020). Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats. The Journal of Surgical Research, 255, 510-516. https://doi.org/10.1016/j.jss.2020.05.092
Umer A, et al. Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats. J Surg Res. 2020 Jul 3;255:510-516. PubMed PMID: 32629333.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats. AU - Umer,Artur, AU - Ługowska-Umer,Hanna, AU - Schönborn-Kellenberger,Oliver, AU - Korolkiewicz,Paweł K, AU - Sein-Anand,Łukasz, AU - Kuziemski,Krzysztof, AU - Korolkiewicz,Roman P, Y1 - 2020/07/03/ PY - 2020/01/29/received PY - 2020/04/26/revised PY - 2020/05/24/accepted PY - 2020/7/7/pubmed PY - 2020/7/7/medline PY - 2020/7/7/entrez KW - Ischemia-reperfusion injury KW - Nolpitantium KW - SB222200 KW - Saredutant KW - Tachykinins SP - 510 EP - 516 JF - The Journal of surgical research JO - J. Surg. Res. VL - 255 N2 - BACKGROUND: Supraceliac aortic clamping and unclamping produces ischemia-reperfusion (I/R) injury of the splanchnic organs. The protective effects of tachykinin receptor antagonists, SR140333 (NK1 receptor), SR48968 (NK2 receptor), and SB222200 (NK3 receptor), against I/R-induced inhibition of intestinal motility were tested in rats. MATERIAL AND METHODS: The intestinal transit of Evans blue was measured in untreated rats and animals subjected to skin incision, I/R (1 h superior mesenteric artery occlusion followed by 24 h reperfusion) or sham operation. Surgical procedures were conducted under diethyl ether anesthesia. RESULTS: The gastrointestinal transit has not been markedly affected in rats, which were anesthetized or subjected to skin incision in comparison with untreated animals. In contrast, a sham operation and I/R have significantly reduced the intestinal motility. Pretreatment with NK1-3 blockers (SR140333 [3-30 μg/kg]; SR48968 [3-100 μg/kg]; and SB222200 [10-100 μg/kg]) reversed dose dependently the effects of I/R to the level observed after sham operation only. A combination of NK1+NK2+NK3 inhibitors exerted an additive effect compared with NK1 and NK2 antagonists used as single agents. Similarly, combined NK1+NK2 were more effective than NK2 alone. Sham operation and I/R have shifted the in vitro carbachol concentration-response curves to the right in comparison with untreated animals, a phenomenon partially reversed by NK1-NK3 pretreatment. CONCLUSIONS: Single-agent and combined treatment with NK1-3 antagonists markedly attenuated the gastrointestinal dysmotility evoked by I/R injury. The pretreatment with NK3 blocker proved to be the most active in this experimental setting. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/32629333/Tachykinin_Antagonists_Reverse_Ischemia/Reperfusion_Gastrointestinal_Motility_Impairment_in_Rats L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(20)30368-1 DB - PRIME DP - Unbound Medicine ER -