CCK1 central receptor antagonist prevented the intestinal stress symptoms in sheep.

The aim of this study was to determine the influence of mechanically induced duodenal distension (DD) and lorglumide (CCK1 receptor antagonist) premedication on electrical activity of various parts of gastrointestinal (GI) tract and the blood plasma cortisol level in sheep. The influence of lorglumide on the unfavourable effects of duodenal distension (performed with a balloon filled with water--40 and 80 ml; DD40 and DD80) was investigated in this study. These effects in sheep were as follows: the atony of forestomachs and abomasum and the transitory stimulation of myoelectrical activity of small intestine and distal parts of large intestine. The animals, under general anaesthesia, had electrodes inserted into the muscular layers of the organ, the duodenal fistula and (in another group of animals) also the ruminal fistula. Five minute duodenal distension (DD40 and DD80) caused an immediate and complete inhibition of the frequency of spike bursts as well as reticulo-ruminal and abomasal contractions, but also a transitory significant increase of spike bursts of the intestinal wall. The duodenal distension (DD40 and DD80) caused a significant increase of plasma cortisol concentration. Lorglumide did not significantly change the motility of gastrointestinal tract and cortisol concentration, but 10 min after the intracerebroventricular (i.c.v.) infusion in the doses of 1 and 2 mg in toto (i.e. 25 and 50 micrograms/kg B.W.) it decreased the cortisol concentration by 59.7%, as compared with the control values. Lorglumide administered in the above mentioned doses 10 min before the DD40 prevented all signs of intestinal stress and decreased the release of cortisol, but only for 10 min since the beginning of the duodenal distension. It is concluded, that lorglumide--an antagonist of the central CCK1 receptors can be an effective antistressoric agent in the stomach atony caused by the duodenal distension (mechanical-algetic-emotional stress) in sheep.