Lactate supply as a determinant of the distribution of intracellular pH within the hepatic lobule

When isolated livers from starved rats are perfused with lactate at constan t perfusate pH and P-co2, there is a marked gradient of cell pH (pH(i)) alo ng the length of the lobular radius, with periportal cells being substantia lly more alkaline than perivenous cells. In the present studies, the perive nous 21 % of the lobular volume was destroyed by retrograde digitonin perfu sion, and antegrade perfusion restored. pH(i) was determined by P-31-NMR. T he remaining periportal cells, the site of gluconeogenesis from lactate, ha d a substantially higher mean pH(i) (7.42) than did the intact liver (7.23) . When lactate was removed from the perfusate, mean pH(i) decreased to 7.25 . The corresponding concentration of cell bicarbonate fell with a half-time of approximately 5 min. When lactate was re-introduced mean pH(i) rose to 7.34. We conclude that a major contributor to periportal alkalinity under t hese conditions is proton consumption during gluconeogenesis from lactate i ons.