Familial hypophosphatemic rickets and its murine model, Hyp, are characterized by a specific defect in renal inorganic phosphate reabsorption. In Hyp mice the defect has been localized to the proximal tubule brush border membrane and a constitutively enhanced protein kinase C has been demonstrated. Since the latter is activated through the protein G pathway, we have studied phosphatidyl inositol 4,5-bisphosphate metabolism (PIP$ sb2$) in normal (+/Y) and Hyp primary cultures of proximal tubules. At confluence, ($ sp3$H) -myo-inositol labelled cultures were stimulated with calcitriol or parathyroid hormone (PTH) for one minute. Cells were extracted and the aqueous phase was chromatographed on ion exchange resin. The inositol phosphate fractions were counted for radioactivity. For calcitriol, maximal PIP$ sb2$ metabolism occurred at 10$ sp{-11}$ M and 10$ sp{-12}$ M for +/Y and Hyp, respectively. For both cultures, PTH produced a maximum at 10$ sp{-8}$ M. Pertussis toxin alone stimulated +/Y but not Hyp cultures and produced no additive stimulation with calcitriol or PTH in either culture.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27342 |
| Date | January 1997 |
| Creators | Hsia, Ariane. |
| Contributors | Delvin, Edgar (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001565322, proquestno: MQ29717, Theses scanned by UMI/ProQuest. |
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