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Intracellular regulatory cascades: Examples from parathyroid hormone regulation of renal phosphate transport

Intrazelluläre Regulationsmechanismen am Beispiel der Regulation des renalen Phosphattransportes

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Summary

The knowledge about intracellular regulatory cascades in hormone action has increased considerably over the last few years. Receptor occupation at the plasma membrane level results in a production of intracellular messengers, such as cyclic nucleotides (cAMP, cGMP), inositoltrisphosphate (IP3), diacylglycerol (DAG) and a rise in cytosolic calcium concentration. These messengers control the activity of different regulatory mechanisms which operate either in sequence or in parallel to generate the final biological response. In PTH-dependent regulation of renal phosphate transport, cAMP-dependent and calcium-dependent mechanisms are involved: Recent experiments with cultured renal epithelial cells have confirmed that activation of adenylate cyclase is the initial event. However, the cAMP signal can be bypassed and direct activation of protein kinase C seems to mimic PTH induced inhibition of phosphate transport. The final event in the regulatory cascade is most likely a removal of the phosphate transport system followed by a degradation.

Zusammenfassung

Die Kenntnisse der intrazellulären Regulationsmechanismen in Hormon-kontrollierten Zell-Funktionen sind während der letzten Jahre enorm angewachsen. Die Besetzung des Rezeptors in der Plasma-Membran führt zur Bildung verschiedener intrazellulärer Signale („Messenger“), z.B. cyclische Nucleotide (cAMP, cGMP), Inositoltrisphosphate (IP3), Diacylglycerin (DAG), Erhöhung der Kalzium-Konzentration. Diese „Messenger“ kontrollieren die Aktivität verschiedener Regulationsmechanismen, die entweder sich folgend oder parallel schlußendlich zur biologischen Antwort führen. Bei der PTH-abhängigen Regulation des Phosphattransportes sind cAMP-abhängige und Kalzium-abhängige Regulationsmechanismen beteiligt: Versuche an kultivierten Epithelzellen haben bestätigt, daß die Stimulierung der Adenylatcyclase als erstes Ereignis auftritt. Das cAMP Signal kann jedoch umgangen werden und eine direkte Aktivierung der Proteinkinase C kann die PTH-Hemmung nachahmen. Als letztes Ereignis in der Regulationskette tritt vermutlich eine Entfernung des Transportsystemes auf.

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  1. Physiologisches Institut der Universität Zürich, Switzerland

    H. Murer & K. Malmström

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  1. H. Murer
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  2. K. Malmström
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Murer, H., Malmström, K. Intracellular regulatory cascades: Examples from parathyroid hormone regulation of renal phosphate transport. Klin Wochenschr 64, 824–828 (1986). https://doi.org/10.1007/BF01725554

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