TRANSFORMING GROWTH-FACTOR-BETA MODULATES THE PARATHYROID HORMONE-RELATED PROTEIN-INDUCED RESPONSES IN RENAL EPITHELIAL-CELLS

PTH-related protein (PTHrP), the major mediator of hypercalcemia of ma lignancy, reduces tubular phosphate (Pi) reabsorption through its PTH- like renotropic actions. Another peptide detected in tumoral cells, tr ansforming growth factor-beta (TGFbeta), has been shown to considerabl y suppress the sodium-dependent Pi transport system present in the api cal membrane of renal epithelial cells. The unexplored interactions be tween TGFbeta and PTHrP were examined in opossum kidney (OK) cells. Us ing confluent OK cells, we showed that TGFbeta attenuated the inhibiti on of Pi transport mediated by PTHrP. Similarly, 18 h TGFbeta incubati on resulted in a substantial reduction of the cAMP response elicited b y PTHrP without apparent involvement of pertussis toxin-sensitive guan ine nucleotide binding protein(s). The number of PTHrP(1-34) binding s ites in TGFbeta-treated cells was decreased with the affinity unchange d. Forskolin- and prostaglandin E2-stimulated cAMP productions were no t significantly altered by TGFbeta treatment. Therefore, TGFbeta reduc ed Pi transport in OK cells, modulated the actions of PTHrP, and decre ased its receptor number. Whether this happens in vivo is as yet unkno wn.