INHIBITION BY CYCLIC-AMP AND PHORBOL ESTERS OF SODIUM-DEPENDENT UPTAKE OF PHOSPHATE BY RAT HEPATOCYTES

Na+-dependent phosphate uptake by rat hepatocytes in primary culture is inhibited in a time-dependent fashion by cyclic AMP and by the myristate, acetate ester of phorbol. After incubation for 15 min at 37-degrees-C with 10(-7) M dibutyryl cAMP, the V(max) of transport is decreased from 0.52 to 0.23 nmol P(i)/min per mg protein but the K(m) value of approximately 1 mM is hardly affected by the treament. Thus, physiological control of P(i) uptake by liver cells probably involves protein phosphorylation(s) catalysed by protein kinases. Protein kinase C may be important but the relatively high concentration of phorbol ester needed to cause inhibition of transport is not convincing evidence for protein kinase C involvent. In the presence of fructose, the rate of P(i) uptake is decreased by 50%. This effect is probably secondary to a depletion of cellular ATP.