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Parathyroid hormone increases cytosolic calcium in neonatal nephron through protein kinase C pathway

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Abstract

In mammals, neonatal positive calcium balance is required for adequate growth. Parathyroid hormone (PTH) plays a central role in this process mainly through its action on the distal nephron. We studied the effect of PTH on cytosolic calcium in distal segments from neonatal rat kidney. PTH elicited a concentration-dependent increase in cytosolic calcium in neonatal distal nephron (EC50=0.5 nM) but not in proximal tubules. At similar PTH concentrations the response was higher in the neonatal than in the adult tubules. The response was associated with protein kinase C (PKC), since phorbol myristate acetate (100 nM) increased [Ca2+]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca2+]i. The response was diminished in low external calcium (0.1 mM) and absent at zero calcium, indicating dependency on external calcium. Resting calcium decreased from 80±10.8 to 28.6±2.6 nM at zero [Ca2+]e. PTH and nifedipine increased cytosolic calcium in an additive fashion. We show for the first time that PTH increased cytosolic calcium in the distal nephron of neonatal kidney, in a concentration-dependent pattern and in association with PKC activation. Higher sensitivity of the neonatal tubule might facilitate absorption of this cation during the neonatal period, when growth requires a positive balance of calcium.

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Acknowledgements.

This study was partially supported by a grant from the Program ECOS-ANUIES for scientific collaboration France-Mexico (Project M96-B02). Dr. Laura Valencia was a recipient of a postgraduate fellowship from Secretaría de Educación Pública, México. The authors gratefully acknowledge the critical review of this material by Dr. M. Cereijido from the Department of Physiology and Biophysics at the Research Center for Advanced Studies. We also acknowledge the technical assistance of Gerardo Sierra and the secretarial support of Elvia Hernandez. Partial support of Conacyt 334511M.

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Authors and Affiliations

  1. Department of Physiology, Biophysics, and Neurosciences, Research Center for Advanced Studies, D.F.07000, Mexico

    Laura Valencia, María C. Namorado, Dolores Martin & Jose L. Reyes

  2. UMR CNRS 6548, Université de Nice, Cedex 2, Nice, France

    Michel Bidet & Philippe Poujeol

  3. Department of Pharmacy, National School of Biological Sciences, National Polytechnic Institute, México

    Estela Melendez

  4. Department of Physiology and Biophysics, Centro de Investigación y de Estudios Avanzados, P.O. Box 14–740, D. F. 07000, México

    Jose L. Reyes

Authors
  1. Laura Valencia
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  2. Estela Melendez
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  3. María C. Namorado
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  4. Dolores Martin
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  5. Michel Bidet
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  6. Philippe Poujeol
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  7. Jose L. Reyes
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Correspondence to Jose L. Reyes.

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Valencia, L., Melendez, E., Namorado, M.C. et al. Parathyroid hormone increases cytosolic calcium in neonatal nephron through protein kinase C pathway. Pediatr Nephrol 19, 1093–1101 (2004). https://doi.org/10.1007/s00467-004-1542-9

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  • DOI: https://doi.org/10.1007/s00467-004-1542-9

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