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cAMP-dependent and -independent downregulation of type II Na-Pi cotransporters by PTH

cAMP-dependent and -independent downregulation of type II Na-Pi cotransporters by PTH Abstract Parathyroid hormone (PTH) leads to the inhibition of Na-P i cotransport activity and to the downregulation of the number of type II Na-P i cotransporters in proximal tubules, as well as in opossum kidney (OK) cells. PTH is known also to lead to an activation of adenylate cyclase and phospholipase C in proximal tubular preparations, as well as in OK cells. In the present study, we investigated the involvement of these two regulatory pathways in OK cells in the PTH-dependent downregulation of the number of type II Na-P i cotransporters. We have addressed this issue by using pharmacological activators of protein kinase A (PKA) and protein kinase C (PKC), i.e., 8-bromo-cAMP (8-BrcAMP) and β-12- O -tetradecanoylphorbol 13-acetate (β-TPA), respectively, as well as by the use of synthetic peptide fragments of PTH that activate adenylate cyclase and/or phospholipase C, i.e., PTH-(1–34) and PTH-(3–34), respectively. Our results show that PTH signal transduction via cAMP-dependent, as well as cAMP-independent, pathways leads to a membrane retrieval and degradation of type II Na-P i cotransporters and, thereby, to the inhibition of Na-P i cotransport activity. Thereby, the cAMP-independent regulatory pathway leads only to partial effects (∼50%). opossum kidney cells protein kinase A protein kinase C phorbol ester parathyroid hormone-(3–34) Footnotes Address for reprint requests and other correspondence: J. Biber, Institute of Physiology, Univ. Zürich-Irchel, Winterthurerstr. 190, CH-8057 Zürich, Switzerland (E-mail: biber@physiol.unizh.ch ). This work was financially supported by Swiss National Science Foundation Grant 31.46523 (to H. Murer). Antibodies against OK cell Na-P i cotransporter protein were a generous gift from E. Lederer. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1999 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Renal Physiology The American Physiological Society

cAMP-dependent and -independent downregulation of type II Na-Pi cotransporters by PTH

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6127
eISSN
1522-1466
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Abstract

Abstract Parathyroid hormone (PTH) leads to the inhibition of Na-P i cotransport activity and to the downregulation of the number of type II Na-P i cotransporters in proximal tubules, as well as in opossum kidney (OK) cells. PTH is known also to lead to an activation of adenylate cyclase and phospholipase C in proximal tubular preparations, as well as in OK cells. In the present study, we investigated the involvement of these two regulatory pathways in OK cells in the PTH-dependent downregulation of the number of type II Na-P i cotransporters. We have addressed this issue by using pharmacological activators of protein kinase A (PKA) and protein kinase C (PKC), i.e., 8-bromo-cAMP (8-BrcAMP) and β-12- O -tetradecanoylphorbol 13-acetate (β-TPA), respectively, as well as by the use of synthetic peptide fragments of PTH that activate adenylate cyclase and/or phospholipase C, i.e., PTH-(1–34) and PTH-(3–34), respectively. Our results show that PTH signal transduction via cAMP-dependent, as well as cAMP-independent, pathways leads to a membrane retrieval and degradation of type II Na-P i cotransporters and, thereby, to the inhibition of Na-P i cotransport activity. Thereby, the cAMP-independent regulatory pathway leads only to partial effects (∼50%). opossum kidney cells protein kinase A protein kinase C phorbol ester parathyroid hormone-(3–34) Footnotes Address for reprint requests and other correspondence: J. Biber, Institute of Physiology, Univ. Zürich-Irchel, Winterthurerstr. 190, CH-8057 Zürich, Switzerland (E-mail: biber@physiol.unizh.ch ). This work was financially supported by Swiss National Science Foundation Grant 31.46523 (to H. Murer). Antibodies against OK cell Na-P i cotransporter protein were a generous gift from E. Lederer. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1999 the American Physiological Society

Journal

AJP - Renal Physiology – The American Physiological Society

Published: May 1, 1999

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