| First Author | Zhao N | Year | 2000 |
| Journal | Endocrinology | Volume | 141 |
| Issue | 6 | Pages | 2159-65 |
| PubMed ID | 10830304 | Mgi Jnum | J:108816 |
| Mgi Id | MGI:3624921 | Doi | 10.1210/endo.141.6.7484 |
| Citation | Zhao N, et al. (2000) Npt2 gene disruption confers resistance to the inhibitory action of parathyroid hormone on renal sodium-phosphate cotransport. Endocrinology 141(6):2159-65 |
| abstractText | PTH inhibition of renal sodium-phosphate (Na-Pi) cotransport is associated with the endocytic retrieval of the type II Na-Pi cotransporter, Npt2, from the renal brush border membrane into the late endosomal/lysosomal compartment. The aim of the present study was to determine whether mice homozygous for the disrupted Npt2 gene (Npt2-/-) exhibit decreased renal Pi reabsorption in response to PTH. We demonstrate that PTH has no effect on the serum Pi concentration, fractional excretion of Pi, or Na-dependent Pi transport in renal brush border membrane vesicles in Npt2-/- mice. In contrast, PTH elicits a fall in the serum Pi concentration, an increase in urinary Pi excretion, a decrease in brush border membrane Na-Pi cotransport, and a corresponding reduction in the relative abundance of Npt2 protein in wild-type mice (Npt2+/+). Both Npt2-/- and Npt2+/+ mice exhibit a significant rise in the urinary cAMP/creatinine ratio in response to PTH, indicating that generalized resistance to PTH cannot account for the absence of the PTH response in Npt2-/- mice. In addition, we demonstrate that Pi-depleted normal mice respond to PTH with a decrease in renal brush border membrane Na-Pi cotransport and Npt2 protein, indicating that Pi deficiency per se does not account for PTH resistance in Npt2-/- mice. Taken together, our data provide compelling evidence that Npt2 gene expression is crucial for PTH effects on renal Pi handling. |
