Aggravation of chemically-induced injury in perfused rat liver by extracellular ATP

The effects of purinergic receptor agonists on acute liver damage and hemodynamics were studied using chemically-induced liver injury. Rat livers were perfused in situ 24 h after treatment with D-galactosamine (800 mg/kg, i.p.). In these livers, infusion of ATP (50 mu M) into the portal vein caused a rapid increase in the leakage of LDH and AST from perfused liver in a dose dependent manner, accompanied with flow reduction. The similar but less effective responses were also observed by the infusion of ADP. Infusion of adenosine, a P-1-receptor agonist, induced only minimal changes of liver damage and flow rate. The ATP-induced changes were almost completely suppressed by P-2-receptor antagonist, suramin, but not affected by P-1-receptor antagonist, 8-phenyltheophylline. Pretreatment of rats with gadolinium chloride, which depletes Kupffer cells, did not inhibit the potentiation of liver damage caused by ATP, whereas hemodynamic effects of ATP were significantly attenuated by gadolinium. These results indicate that extracellular ATP aggravates acute liver injury mediated by P-2-type purinergic receptors.