title: Increased prostaglandin I2 and thromboxane A2 production by rat dental pulp after intravenous administration of endotoxin.
abstract: The effect of systemic endotoxin (lipopolysaccharide from Escherichia coli 0111:B4) on prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) production by rat dental pulp was investigated. Intravenous injection of endotoxin increased ex vivo production of both PGI2 and TXA2 by the pulp tissue, when determined by radioimmunoassay. A significant effect on PGI2 and TXA2 production was observed with endotoxin doses of greater than 2 and 0.4 mg/kg, respectively. A significant increase was also observed at 30 min after injection of 10 mg/kg endotoxin, reaching a maximum after 60 min for both PG and TX production. Endotoxin (10 mg/kg for 60 min) also increased TXA2 but not PGI2 production in lung tissue, but had no effect in jejunal tissue. Indomethacin (10 microM) completely inhibited PGI2 and TXA2 production by the pulp of physiological saline- and endotoxin-treated rats. Further, arachidonic acids (10 microM) significantly increased PG and TX production by the pulp of saline- but not of endotoxin-treated rats. Endotoxin (100 micrograms/ml) had no in vitro effect on PG or TX production when incubated with isolated pulp, lung and jejunal tissues, suggesting that the endotoxin-induced increases in PG and TX production are an indirect effect. The endotoxin-induced increase in TXA2 production, but not in PGI2 production, by the pulp tissue was significantly suppressed by WEB 2170, a platelet-activating factor (PAF) antagonist. These results indicate that arachidonate metabolism in pulp tissue is susceptible to endotoxaemia in comparison with the lung and jejunum, and further suggest that the endotoxin-induced increase in, at least, TXA2 production by the pulp is mediated by PAF.
authors.affiliation: Department of Pharmacology, Tohoku University School of Dentistry, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirafuji
authors.forename: H
authors.initials: H
authors.lastname: Shinoda
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology; D003782:Dental Pulp / Q000187:drug effects / Q000378:metabolism*; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004926:Escherichia coli; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007583:Jejunum / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D004731:Endotoxins; D010972:Platelet Activating Factor; D014230:Triazoles; D016718:Arachidonic Acid; D013928:Thromboxane A2; C063964:bepafant; D011464:Epoprostenol; D007213:Indomethacin