Beta 2-adrenergic agonist regulation of immune aggregate- and platelet-activating factor-stimulated hepatic metabolism.
Vasoconstriction and subsequent glycogenolysis stimulated by immune complex infusion into perfused rat livers was inhibited by prior infusion of isoproterenol. Similarly, isoproterenol inhibited the biosynthesis of bioactive lipid autacoids such as platelet-activating factor, prostaglandin E2, and thromboxane B2 which was stimulated by immune aggregates. The adrenergic receptor specificity of these effects was determined through the use of specific adrenergic subtype-specific agonists and antagonists to be mediated by beta 2-adrenergic receptors. Indirect evidence for the differential expression of hepatic sinusoidal and parenchymal beta-adrenergic receptors in the male rat during ontogeny suggested that inhibition of immune aggregate-stimulated autacoid biosynthesis, vasoconstriction, and glycogenolysis by isoproterenol occurs at a sinusoidal locus, most likely Kupffer cells. In contrast with the ability of beta 2-adrenergic agonists to inhibit immune aggregate- and platelet-activating factor-stimulated hepatic metabolism, dibutyryl cyclic AMP did not mimic these sinusoidal beta 2-adrenergic effects, despite stimulating hepatic parenchymal cell glycogenolysis as effectively as isoproterenol. These observations suggest a role for cyclic AMP-independent mechanisms in the regulation of heterologous stimulus-response coupling by hepatic sinusoidal beta 2-adrenergic receptors.
Steinhelper
M E
ME
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Fisher
R A
RA
Revtyak
G E
GE
Hanahan
D J
DJ
Olson
M S
MS
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D003994:Bucladesine / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D006003:Glycogen / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010972:Platelet Activating Factor / Q000096:biosynthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013929:Thromboxane B2 / Q000096:biosynthesis; D014661:Vasoconstriction
D000936:Antigen-Antibody Complex; D010972:Platelet Activating Factor; D011943:Receptors, Adrenergic, beta; D013929:Thromboxane B2; D003994:Bucladesine; D006003:Glycogen; D015232:Dinoprostone; D007545:Isoproterenol