Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHRP) regulate Na$ sp+$/H$ sp+$ exchanger (NHE) activity in various types of cells such as osteoblastic cells and renal proximal tubule OK cells. Na$ sp+$/H$ sp+$ exchangers are plasma membrane transporters catalyzing the electroneutral exchange of 1 H$ sp+$ for 1 Na$ sp+.$ Several mammalian isoforms of NHE have been so far identified with each mediating a variety of specific functions. Parathyroid hormone, playing an essential role in the physiology of blood Ca$ sp{2+}$ and phosphate homeostasis, inhibits renal proximal tubular bicarbonate reabsorption by inhibiting the apically located Na$ sp+$/H$ sp+$ exchanger. However, which specific isoform of NHE mediated this effect and the specific signaling components involved were unknown. In our studies we determined that Na$ sp+$/H$ sp+$ exchanger NHE-3 isoform is expressed in the renal proximal tubule OK cells and that N-terminal PTH and PTHRP analogues upon binding to their receptor stimulate both the PKA and the PKC pathways, each of which can independently lead to inhibition of this exchanger activity. NHEs also play an important role in the regulation of intracellular pH which is subject to fluctuation occurring during the process of hormone stimulated bone formation and bone remodeling. Again the specific NHE isoform(s) mediating this effect and the signaling pathways involved were unidentified. It is determined by our studies that NHE type 1 is expressed in osteoblastic cell line, UMR-106 cells, and that PTH and PTHRP stimulate this exchanger via a cAMP-dependent pathway exclusively. It was believed that motivation of NHE-1 in the UMR-106 cells and inhibition of NHE-3 in the OK cells by N-terminal analogues of PTH and PTHRP involves binding of these analogues to a common G protein-coupled receptor called the "classical" PTH/PTHRP receptor. However, with the recent discovery of other PTH and/or PTHRP receptor, this hypothesis is no longer clear
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.40109 |
| Date | January 1996 |
| Creators | Azarani, Arezou |
| Contributors | D., Goltzman (advisor), J., Orlowski (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 | Doctor of Philosophy (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001496127, proquestno: NN12327, Theses scanned by UMI/ProQuest. |
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