Abstract
PTH-related protein (PTHrP), the major mediator of hypercalcemia of malignancy, reduces tubular phosphate (Pi) reabsorption through its PTH-like renotropic actions. Another peptide detected in tumoral cells, transforming growth factor-beta (TGF beta), has been shown to considerably suppress the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. The unexplored interactions between TGF beta and PTHrP were examined in opossum kidney (OK) cells. Using confluent OK cells, we showed that TGF beta attenuated the inhibition of Pi transport mediated by PTHrP. Similarly, 18 h TGF beta incubation resulted in a substantial reduction of the cAMP response elicited by PTHrP without apparent involvement of pertussis toxin-sensitive guanine nucleotide binding protein(s). The number of PTHrP(1-34) binding sites in TGF beta-treated cells was decreased with the affinity unchanged. Forskolin- and prostaglandin E2-stimulated cAMP productions were not significantly altered by TGF beta treatment. Therefore, TGF beta reduced Pi transport in OK cells, modulated the actions of PTHrP, and decreased its receptor number. Whether this happens in vivo is as yet unknown.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
