Stimulation of glycogenolysis and platelet-activating factor production by heat-aggregated immunoglobulin G in the perfused rat liver.

Infusion of heat-aggregated immunoglobulin G (IgG) into perfused livers from fed rats resulted in a dose-dependent but transient stimulation of hepatic glucose output. Oxygen consumption and lactate production by the liver also were stimulated, while the lactate/pyruvate ratio of the effluent perfusate was increased. Upon return of hepatic glucose output to the basal rate following immune aggregate stimulation, a second infusion of immune aggregate caused little or no increase in glucose output, indicating desensitization of the response. Infusion of immune aggregate into rat livers also resulted in the appearance of platelet-activating factor activity in the effluent perfusate. Synthetic platelet-activating factor or acetylglyceryl ether phosphorylcholine (AGEPC) has been demonstrated to be a potent glycogenolytic agonist in the perfused liver (Buxton, D.B., Shukla, S. D., Hanahan, D. J., and Olson, M.S. (1984) J. Biol. Chem. 259, 1468-1471). The glycogenolytic response of the liver to immune aggregate infusion was not desensitized by prior infusion of AGEPC. Co-infusion of the cyclooxygenase inhibitor indomethacin prevented the immune aggregate-induced glycogenolytic response but had no effect on AGEPC-stimulated hepatic glucose output. It is suggested that the mechanism by which aggregated IgG activates hepatic glycogenolysis requires the synthesis of AGEPC by the liver by a pathway which involves the metabolism of arachadonic acid.