Characterization of lipopolysaccharide-induced emesis in conscious piglets: effects of cervical vagotomy, cyclooxygenase inhibitors and a 5-HT(3) receptor antagonist.
The emetic response to intraperitoneal (i.p., 0.5, 2, 8 mg kg(-1)) and intravenous (i.v., 200 microg kg(-1)) administration of bacterial lipopolysaccharides (LPS) was characterized in conscious piglets observed for 4 h. The latencies and the incidence of the emetic response to LPS (i.p.) decreased and increased, respectively, in a dose-dependent manner. In 14 additional piglets, a bilateral vagotomy performed 4 h prior to LPS administration abolished the vomiting induced by i.p. LPS (2 mg kg(-1)), and decreased its incidence by 77% in the i.v. injected animals. Sham-operated animals (n=6) exhibited a similar emetic pattern to the controls injected intraperitoneally with LPS (2 mg kg(-1)). In 7 piglets, the administration of granisetron, a 5-HT(3) receptor antagonist (i.v., 2 mg kg(-1)), 30 min prior to the i.p. LPS injection (2 mg kg(-1)) failed to reduce significantly the emetic activity; whereas, in 6 animals, a combination of meloxicam (0.3 mg kg(-1)) and indomethacin (5 mg kg(-1)), two cyclooxygenase (COX) inhibitors, administered per os 1.5 h prior to the i.p. LPS (2 mg kg(-1)) abolished the emetic response to endotoxins. The present results show that the activation of the medullary "vomiting centre" in response to i.p. administration of LPS is mediated via vagal afferents and is likely to involve prostaglandins.
Girod
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Laboratoire de Neurobiologie et Neurophysiologie Fonctionnelles, Département de Physiologie et Neurophysiologie (ESA CNRS 6034), Université d'Aix-Marseille III, Faculté des Sciences et Techniques St Jérôme, Case 351, 13397 cedex 20, Marseil, France.
Bouvier
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Grélot
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D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017829:Granisetron / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D000077239:Meloxicam; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012803:Sick Role; D013552:Swine; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014628:Vagotomy; D014839:Vomiting / Q000139:chemically induced*
D000932:Antiemetics; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D017829:Granisetron; D007213:Indomethacin; D007527:Isoenzymes; D008070:Lipopolysaccharides; D000077239:Meloxicam; D011451:Prostaglandin-Endoperoxide Synthases; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D013843:Thiazines; D013844:Thiazoles