Leukotriene C4 metabolism during its action on glucose and lactate balance and flow in perfused rat liver.

Rat livers were perfused in a non-recirculating mode at constant pressure via the portal vein with media containing 5 mM glucose, 2 mM lactate, and 0.2 mM pyruvate. [3H]LTC4 was infused for a period of 5 min to a final concentration of 20 nM; it increased glucose and lactate output and reduced perfusion flow. 1) Leukotriene radioactivity was recovered 10 min after the onset of [3H]LTC4 infusion to about 40% in the effluent, to 20% in the bile, and to 40% in the liver. 2) Radioactivity in the effluent increased to a maximum 4-5 min after the onset and decreased again to essentially zero 3 min after completion of [3H]LTC4 infusion. [3H]LTC4 and [3H]LTD4 were the major labeled components in the effluent accounting for 45% and 38%, respectively, of the effluent radioactivity. 3) [3H]LTC4 and [3H]LTD4 were also the major components in bile; they accounted for 50% and 30%, respectively, of the radioactivity excreted, while more polar [3H]leukotriene metabolites accounted for the remainder. 4) In the liver, [3H]LTC4 and [3H]LTD4 were the major and [3H]LTE4, N-acetyl-[3H]LTE4 as well as omega-hydroxy-N-acetyl-[3H]LTE4 and omega-carboxy-N-acetyl-[3H]LTE4 were minor components detected 5 min after completion of [3H]LTC4 infusion. It is concluded from the present findings that during a 5 min infusion period about one third each of the infused LTC4 remained unchanged, was converted to LTD4, and was further degraded to LTE4 and polar metabolites including omega-oxidation products of N-acetyl-LTE4.(ABSTRACT TRUNCATED AT 250 WORDS)