Signaling pathways utilized by PTH and dopamine to inhibit phosphate transport in mouse renal proximal tubule cells
Autor: | Shirish Shenolikar, Rochelle Cunningham, Edward J. Weinman, Deborah Steplock, Rajatsubhra Biswas, Marc F. Brazie |
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Rok vydání: | 2009 |
Předmět: |
Male
Physiology Dopamine Enzyme Activators Parathyroid hormone Protein Serine-Threonine Kinases Biology Phosphates Kidney Tubules Proximal Mice Enzyme activator Cyclic AMP medicine Animals Enzyme Inhibitors Cells Cultured Protein kinase C Phosphate transport Protein-Serine-Threonine Kinases Articles Mice Inbred C57BL medicine.anatomical_structure Biochemistry Parathyroid Hormone Proximal tubule Signal transduction hormones hormone substitutes and hormone antagonists Signal Transduction medicine.drug |
Zdroj: | American Journal of Physiology-Renal Physiology. 296:F355-F361 |
ISSN: | 1522-1466 1931-857X |
DOI: | 10.1152/ajprenal.90426.2008 |
Popis: | 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. |
Databáze: | OpenAIRE |
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