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


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.
Department of Internal Medicine and Toxicology, Medical University of Gdańsk, Debinki 7, 80-211 Gdańsk, Poland.
R
R
Ciechanownicz
J
J
Sein-Anand
Z
Z
Chodorowski
M
M
Bitel
J
J
Petrusewicz
R P
RP
Korolkiewicz
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D004195:Disease Models, Animal; D004986:Ether / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011183:Postoperative Complications / Q000188:drug therapy* / Q000517:prevention & control*; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*
D018685:Anesthetics, Inhalation; D014150:Antipsychotic Agents; D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; D004986:Ether; C085215:SR 140333; C073839:SR 48968; C091554:SR 142801