Regulation of hepatic glycogenolysis and vasoconstriction during antigen-induced anaphylaxis.
Effects of sensitizing antigen (ovalbumin) on various physiological and hepatic parameters were investigated in sensitized rats and isolated perfused livers derived from sensitized rats. Administration of ovalbumin (500 micrograms) to the portal venous circulation of sensitized but not nonsensitized rats resulted in a rapid and sustained decrease in systemic arterial pressure, characteristic of antigen-induced anaphylaxis, and pronounced increases in hepatic portal pressure and blood glucose concentration. These antigen-mediated alterations were similar to those observed in response to platelet-activating factor (PAF) (0.1 micrograms/kg) administration to rats and were inhibited significantly by specific PAF receptor antagonist WEB 2086 (250 micrograms/kg). Infusion of ovalbumin (3.8 micrograms/ml) into isolated perfused livers derived from sensitized rats resulted in significant increases in hepatic glucose output and portal pressure and decreases in oxygen consumption, as observed in response to PAF (0.28 nM) infusion into perfused livers. These hepatic responses to ovalbumin were antigen specific and were not observed in nonsensitized rat perfused livers. Hemodynamic and glycogenolytic responses to ovalbumin in perfused livers were inhibited significantly but less effectively than similar responses to PAF by infusion of WEB 2086 (500 nM) into livers. Coinfusion of indomethacin (2.8 microM) and nordihydroguariatic acid (1 microM) with WEB 2086 (500 nM) into perfused livers inhibited further hemodynamic but not glycogenolytic responses to ovalbumin. Infusion of nitric oxide (34 microM) into sensitized rat perfused livers prevented the hemodynamic and glycogenolytic responses to both ovalbumin and PAF. These observations provide evidence that hepatic glycogenolysis and vasoconstriction are stimulated during antigen-induced anaphylaxis and suggest that these responses are mediated in part by PAF.
Hines
K L
KL
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Fisher
R A
RA
D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001381:Azepines / Q000494:pharmacology; D015777:Eicosanoids / Q000037:antagonists & inhibitors; D000939:Epitopes; D005260:Female; D006003:Glycogen / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000941:Antigens; D001381:Azepines; D015777:Eicosanoids; D000939:Epitopes; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D009569:Nitric Oxide; D006003:Glycogen; D010047:Ovalbumin