Characterization of lipopolysaccharide-induced emesis in conscious piglets: effects of cervical vagotomy, cyclooxygenase inhibitors and a 5-HT3 receptor antagonist

The emetic response to intraperitoneal (i.p., 0.5, 2, 8 mg kg(-1)) and intr avenous (i.v., 200 mu g kg(-1)) administration of bacterial lipopolysacchar ides (LPS) was characterized in conscious piglets observed for 4 h. The lat encies and the incidence of the emetic response to LPS (i.p.) decreased and increased, respectively, in a dose-dependant manner. In 14 additional pigl ets, a bilateral vagotomy performed 4 h prior to LPS administration abolish ed the vomiting induced by i.p. LPS (2 mg kg(-1)), and decreased its incide nce by 77% in the i.v. injected animals. Sham-operated animals (n=6) exhibi ted a similar emetic pattern to the controls injected intraperitoneally wit h LPS (2 mg kg(-1)). In 7 piglets, the administration of granisetron, a 5-H T3 receptor antagonist (i.v., 2 mg kg(-1)). 30 min prior to the i.p. LPS in jection (2 mg kg(-1)) failed to reduce significantly the emetic activity; w hereas, in 6 animals, a combination of meloxicam (0.3 mg kg(-1)) and indome thacin (5 mg kg(-1)), two cyclooxygenase (COX) inhibitors, administered per os 1.5 h prior to the i.p. I,PS (2 mg kg(-1)) abolished the emetic respons e to endotoxins. The present results show that the activation of the medull ary "vomiting centre" in response to i.p. administration of LPS is mediated via vagal afferents and is likely to involve prostaglandins. (C) 2000 Else vier Science Ltd. All rights reserved.