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Published on: October 28, 2014
Parathyroid hormone increases cytosolic calcium in neonatal nephron through protein kinase C pathway
Laura Valencia1, Estela Melendez, María C Namorado
1Department of Physiology, Biophysics, and Neurosciences, Research Center for Advanced Studies, D.F.07000, Mexico.
Insights
Parathyroid hormone (PTH) increases calcium in neonatal rat kidney's distal nephron, a process linked to protein kinase C (PKC). This higher sensitivity in newborns aids calcium absorption for growth.
Area of Science:
- Nephrology
- Pediatric Endocrinology
- Calcium Homeostasis
Background:
- Neonatal growth necessitates a positive calcium balance in mammals.
- Parathyroid hormone (PTH) is crucial for calcium regulation, primarily acting on the kidney's distal nephron.
- Understanding PTH's role in neonatal kidney calcium handling is vital for growth and development.
Purpose of the Study:
- To investigate the effect of PTH on cytosolic calcium levels in distal kidney tubules of neonatal rats.
- To determine the concentration-dependency and signaling pathways involved in PTH-induced calcium changes.
- To compare the neonatal kidney's response to PTH with that of adult kidneys.
Main Methods:
- Studied cytosolic calcium ([Ca(2+)]i) in isolated neonatal rat kidney distal tubule segments.
- Administered varying concentrations of PTH and measured [Ca(2+)]i.
- Utilized phorbol myristate acetate and staurosporin to probe the involvement of protein kinase C (PKC).
- Assessed the impact of external calcium concentrations and cAMP analogues on the PTH response.
Main Results:
- PTH caused a concentration-dependent increase in cytosolic calcium in neonatal distal tubules (EC(50)=0.5 nM), but not in proximal tubules.
- The response in neonatal tubules was significantly higher than in adult tubules at similar PTH concentrations.
- The PTH effect was mediated by PKC activation and dependent on external calcium availability.
- PTH and nifedipine demonstrated additive effects on cytosolic calcium.
Conclusions:
- PTH elevates cytosolic calcium in the neonatal rat kidney distal nephron via a PKC-dependent pathway.
- The heightened sensitivity of the neonatal distal tubule to PTH may facilitate enhanced calcium absorption during critical growth periods.
- This mechanism is essential for maintaining the positive calcium balance required for neonatal development.
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(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(2+)]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca(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(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.
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