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Enzymological and cellular mechanisms of parathyroid hormone degradation by the kidney

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Abstract

Parathyroid hormone (PTH) is known to be degraded in the kidney at both the luminal microvilli and the basolateral surfaces of the proximal renal tubulesin vivo. We have recently isolated a PTH-degrading enzyme from the microvillar membranes of rat kidney. The NH2-terminal amino acid sequence of the purified enzyme was identical to meprin (EC 3, 4, 24, 18). Both the microvillar membrane preparation and purified enzyme generated PTH cleavage peptides that have similar sequences. These results clearly show that the PTH-degrading microvillar enzyme is meprin. We also have investigated the cellular mechanisms of PTH-degradation at the basolateral surfaces using the cultured cell line from the proximal renal tubules, opossum kidney (OK) cells, which have a functional PTH receptor but lack luminal microvilli. The results suggest that this process is largely dependent on a receptor-mediated endocytosis and subsequent lysosomal hydrolysis and partially on a hydrolytic activity by a chymotrypsin-like endopeptidase in the membranes. The experiments using phorbol esters suggest that the latter activity might be augmented by protein kinase C activation.

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Authors and Affiliations

  1. Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, 650, Kobe, Japan

    Toru Yamaguchi M.D., Masaaki Fukase, Toshitsugu Sugimoto & Kazuo Chihara

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  1. Toru Yamaguchi M.D.
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  2. Masaaki Fukase
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  3. Toshitsugu Sugimoto
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  4. Kazuo Chihara
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Yamaguchi, T., Fukase, M., Sugimoto, T. et al. Enzymological and cellular mechanisms of parathyroid hormone degradation by the kidney. J Bone Miner Metab 12 (Suppl 1), S19–S22 (1994). https://doi.org/10.1007/BF02375669

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  • DOI: https://doi.org/10.1007/BF02375669

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