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

Byline: Laura Valencia (1), Estela Melendez (3), Maria C. Namorado (1), Dolores Martin (1), Michel Bidet (2), Philippe Poujeol (2), Jose L. Reyes (1,4) Keywords: cAMP; Phorbol myristate acetate; Parathyroid hormone; Staurosporin; Cycloheximide; Nifedipine; Newborn 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 (EC.sub.50=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 [Ca.sup.2+]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca.sup.2+]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 [Ca.sup.2+]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. Author Affiliation: (1) Department of Physiology, Biophysics, and Neurosciences, Research Center for Advanced Studies, D.F.07000, Mexico (2) UMR CNRS 6548, Universite de Nice, Cedex 2, Nice, France (3) Department of Pharmacy, National School of Biological Sciences, National Polytechnic Institute, Mexico (4) Department of Physiology and Biophysics, Centro de Investigacion y de Estudios Avanzados, P.O. Box 14--740, D. F. 07000, Mexico Article History: Registration Date: 14/05/2004 Received Date: 01/05/2003 Accepted Date: 28/04/2004 Online Date: 05/08/2004