| First Author | Ranieri M | Year | 2015 |
| Journal | J Cell Sci | Volume | 128 |
| Issue | 13 | Pages | 2350-60 |
| PubMed ID | 25977473 | Mgi Jnum | J:232910 |
| Mgi Id | MGI:5780404 | Doi | 10.1242/jcs.168096 |
| Citation | Ranieri M, et al. (2015) Negative feedback from CaSR signaling to aquaporin-2 sensitizes vasopressin to extracellular Ca2. J Cell Sci 128(13):2350-60 |
| abstractText | We previously described that high luminal Ca(2+) in the renal collecting duct attenuates short-term vasopressin-induced aquaporin-2 (AQP2) trafficking through activation of the Ca(2+)-sensing receptor (CaSR). Here, we evaluated AQP2 phosphorylation and permeability, in both renal HEK-293 cells and in the dissected inner medullary collecting duct, in response to specific activation of CaSR with NPS-R568. In CaSR-transfected cells, CaSR activation drastically reduced the basal levels of AQP2 phosphorylation at S256 (AQP2-pS256), thus having an opposite effect to vasopressin action. When forskolin stimulation was performed in the presence of NPS-R568, the increase in AQP2-pS256 and in the osmotic water permeability were prevented. In the freshly isolated inner mouse medullar collecting duct, stimulation with forskolin in the presence of NPS-R568 prevented the increase in AQP2-pS256 and osmotic water permeability. Our data demonstrate that the activation of CaSR in the collecting duct prevents the cAMP-dependent increase in AQP2-pS256 and water permeability, counteracting the short-term vasopressin response. By extension, our results suggest the attractive concept that CaSR expressed in distinct nephron segments exerts a negative feedback on hormones acting through cAMP, conferring high sensitivity of hormone to extracellular Ca(2+). |
