INTRAVENOUS INTERLEUKIN-1-BETA-INDUCED INHIBITION OF GASTRIC-EMPTYING- INVOLVEMENT OF CENTRAL CORTICOTROPIN-RELEASING FACTOR AND PROSTAGLANDIN PATHWAYS IN RATS

The role of corticotrophin-releasing factor (CRF) and prostaglandin in interleukin-1 beta (IL-1 beta)-induced delayed gastric emptying was i nvestigated. Gastric emptying was monitored 20 min after orogastric de livery of a methylcellulose phenol red solution in fasted rats injecte d intravenously with IL-1 beta at the ED(50) dose (3 ng/rat) 30 min be fore the non-caloric solution. The IL-1 receptor antagonist (IL-1 ra) injected intravenously (3 mu g/rat) or intracisternally (100 ng/rat) r eversed the IL-1 beta-induced 47% inhibition of gastric emptying by 10 0% and 62%, respectively. The new CRF antagonist [DPhe(12), Nle(21,38) , C(alpha)MeLeu(37)]-CRF(12-41) (20 mu g/rat), injected intracisternal ly, or indomethacin (5 mg/kg i.p.) completely abolished IL-1 beta (3 n g/rat i.v.)-induced gastric stasis. The CRF antagonist injected intrav enously (20 mu g/rat) did not influence the IL-1 beta inhibitory actio n. None of the pretreatments given alone influenced basal gastric empt ying. These data suggest that peripheral IL-1 beta-induced inhibition of gastric emptying is mediated by specific IL-1 receptor interactions and brain CRF pathways requiring the integrity of eicosanoid-cyclooxy genase pathways.