Regulation of immune-aggregate-stimulated hepatic glycogenolysis and vasoconstriction by vicinal dithiols.
Evidence suggesting that vicinal dithiols regulate immune-aggregate-induced vasoconstriction and glycogenolysis in the perfused rat liver was obtained. Phenylarsine oxide (PhAsO) and other tervalent organic arsenicals inhibited in a dose-dependent manner hepatic glycogenolysis, vasoconstriction, Ca2+ mobilization and the stimulated O2 consumption caused by immune-aggregate infusion. Polar tervalent and quinquivalent arsenicals were less effective than hydrophobic arsenicals. Prior infusion of Fc- but not Fab-fragments of IgG prevented partially immune-aggregate-stimulated hepatic metabolism, suggesting that immune aggregates elicit hepatic metabolic responses through Fc gamma receptors. The inhibitory action of PhAsO on immune-aggregate-stimulated hepatic glycogenolysis was unique; inhibition of glycogenolysis was not observed when phenylephrine, isoprenaline or glucagon was used as a stimulant. Although PhAsO might be expected to sequester cellular thiols, no significant change in the oxidation-reduction state of the major cellular thiol, glutathione, was found during PhAsO infusion. In addition, PhAsO exerted its effects without producing changes in hepatic adenine nucleotides and cyclic AMP. Evidence suggesting the involvement of vicinal dithiols was obtained through thiol-competition experiments using mono- and di-thiols. PhAsO inhibition of IgG-aggregate-stimulated hepatic vasoconstriction and glycogenolysis was reversed significantly by infusion of 2,3-dimercaptopropan-1-ol at 3-fold molar excess, whereas 2-mercaptoethanol at 40-fold molar excess was ineffective. The results of the present study provide evidence documenting the participation of vicinal dithiols during the coupling of hepatic immune-aggregate clearance by Kupffer cells with vasoconstriction of the hepatic vasculature (e.g. endothelial cells) and glycogenolysis (e.g. parenchymal cells).
Steinhelper
M E
ME
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Olson
M S
MS
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001152:Arsenicals / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000096:biosynthesis; D007128:Immunoglobulin Fragments / Q000276:immunology; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000227:Adenine Nucleotides; D000936:Antigen-Antibody Complex; D001152:Arsenicals; D007128:Immunoglobulin Fragments; D008112:Liver Glycogen; D013438:Sulfhydryl Compounds; C029341:oxophenylarsine; D010656:Phenylephrine; D005934:Glucagon; D005947:Glucose; D007545:Isoproterenol; D002118:Calcium