Signaling pathways utilized by PTH and dopamine to inhibit phosphate transport in mouse renal proximal tubule cells.

Published

Journal Article

The present experiments were designed to detail factors regulating phosphate transport in cultured mouse proximal tubule cells by determining the response to parathyroid hormone (PTH), dopamine, and second messenger agonists and inhibitors. Both PTH and dopamine inhibited phosphate transport by over 30%. The inhibitory effect of PTH was completely abolished in the presence of chelerythrine, a PKC inhibitor, but not by Rp-cAMP, a PKA inhibitor. By contrast, both chelerythrine and Rp-cAMP blocked the inhibitory effect of dopamine. Chelerythrine inhibited PTH-mediated cAMP accumulation but also blocked the inhibitory effect of 8-bromo-cAMP on phosphate transport. On the other hand, Rp-cAMP had no effect on the ability of DOG, a PKC activator, to inhibit phosphate transport. PD98059, an inhibitor of MAPK, had no effect on PTH- or dopamine-mediated inhibition of sodium-phosphate cotransport. Finally, compared with 8-bromo-cAMP, 8-pCPT-2'-O-Me-cAMP, an activator of EPAC, had no effect on phosphate transport. These results outline significant differences in the signaling pathways utilized by PTH and dopamine to inhibit renal phosphate transport. Our results also suggest that activation of MAPK is not critically involved in PTH- or dopamine-mediated inhibition of phosphate transport in mouse renal proximal tubule cells in culture.

Full Text

Duke Authors

Cited Authors

  • Cunningham, R; Biswas, R; Brazie, M; Steplock, D; Shenolikar, S; Weinman, EJ

Published Date

  • February 2009

Published In

Volume / Issue

  • 296 / 2

Start / End Page

  • F355 - F361

PubMed ID

  • 18987113

Pubmed Central ID

  • 18987113

International Standard Serial Number (ISSN)

  • 1931-857X

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.90426.2008

Language

  • eng

Conference Location

  • United States