TRANSFORMING GROWTH-FACTOR-BETA INHIBITS PHOSPHATE-TRANSPORT IN RENAL EPITHELIAL-CELLS

The effect(s) of transforming growth factor-beta (TGF-beta) on P(i) transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium-dependent P(i), but not alanine, transport. This selective inhibitory effect on P(i) transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in P(i) uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated P(i) transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced P(i) transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent P(i) transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes.