TRANSFORMING GROWTH-FACTOR-BETA INHIBITS PHOSPHATE-TRANSPORT IN RENALEPITHELIAL-CELLS

The effect(s) of transforming growth factor-beta (TGF-beta) on P(i) tr ansport was investigated in confluent opossum kidney (OK) epithelial c ells. 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 rever sible and was not associated with a rise in adenosine 3',5'-cyclic mon ophosphate production. The reduction in P(i) uptake was also independe nt of changes in extracellular calcium concentrations and prostaglandi n synthesis. TGF-beta-mediated P(i) transport inhibition appeared to i nvolve neither pertussis toxin-sensitive G protein(s) nor augmented pr otein kinase C activity. However, the probable role of a serine/threon ine protein kinase in signal transduction was supported by the conside rable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta -induced P(i) transport reduction was blunted by cycloheximide and abo lished 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 transcription al and translational processes.