Salutary effects of tachykinin receptor antagonists in a rat model of postoperative ileus.

Abstract

BACKGROUND:

Postoperative ileus (PI) is a common surgical complication treated mainly with supportive measures. Tachykinins control gastrointestinal motility and modulate somatic and visceral pain sensation; therefore, the effect of tachykinin receptor antagonists in a rat model of PI using NK(1-3) antagonists, SR140333, SR48968, and SR142801, was investigated.

MATERIALS AND METHODS:

Intestinal transit was measured as Evans blue migration after varied nociceptive stimuli: skin incision (SI), laparotomy (LAP), or laparotomy plus gut manipulation (L + M) in anesthetized rats.

RESULTS:

Diethyl ether anesthesia and SI did not influence the intestinal transit of the dye in comparison to untreated animals--UN: 61.17 +/- 5.47, 62.10 +/- 8.30, and 56.70 +/- 4.10 cm, respectively. In contrast LAP and L + M have significantly reduced intestinal motility to 26.40 +/- 2.07 and 9.70 +/- 1.15 cm, respectively. SR140333 (3-30 microg/kg), SR48968 (1-30 microg/kg), and SR142801 (3-10 microg/kg) reversed the additional inhibitory effects of gut manipulation subsequent to LAP dose-dependently, the dye transit returning with the use of the most effective antagonist doses up to 25.28 +/- 1.08, 21.70 +/- 0.19, and 25.0 +/- 1.34 cm. The combinations of submaximal doses of NK(1) and NK(3), NK(2) and NK(3) and NK(1), and NK(2) and NK(3) antagonists were not more effective than a single-agent regimen. On the other hand SR140333 and SR48968 (NK(1) + NK(2) antagonists) acted additively, the intestinal transit reaching 26.60 +/- 0.85 cm. SR140333, SR48968, and SR142801 have not affected the intestinal passage in UN rats or those undergoing SI or LAP.

CONCLUSIONS:

SR140333, SR48968, and SR142801 exert a salutary action on suppressed gut motility following surgical manipulation of the gut, the combination of NK(1) and NK(2) antagonists being most beneficial.

• Authors: R Ciechanownicz, J Sein-Anand, Z Chodorowski, M Bitel, J Petrusewicz, R P Korolkiewicz
• Journal: The Journal of surgical research (J Surg Res) Vol. 133 Issue 2 Pg. 197-202 (Jun 15 2006) ISSN: 0022-4804 [Print] United States
• PMID: 16487976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Inhalation
• Antipsychotic Agents
• Benzamides
• Neurokinin-1 Receptor Antagonists
• Piperidines
• Quinuclidines
• Receptors, Neurokinin-2
• Receptors, Neurokinin-3
• Receptors, Tachykinin
• Ether
• SR 140333
• SR 48968
• SR 142801

Topics

• Anesthetics, Inhalation (pharmacology)
• Animals
• Antipsychotic Agents (pharmacology)
• Benzamides (pharmacology)
• Disease Models, Animal
• Ether (pharmacology)
• Gastrointestinal Motility (drug effects)
• Ileus (drug therapy, etiology, prevention & control)
• Male
• Neurokinin-1 Receptor Antagonists
• Piperidines (pharmacology)
• Postoperative Complications (drug therapy, prevention & control)
• Quinuclidines (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Neurokinin-2 (antagonists & inhibitors)
• Receptors, Neurokinin-3 (antagonists & inhibitors)
• Receptors, Tachykinin (antagonists & inhibitors)