AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus

Journal: Nature Communications

Published: 2018-04-12

DOI: 10.1038/s41467-018-03771-2

Affiliations: 4

Authors: 11

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Research Highlight

Drugs reverse kidney condition in mice

© ALFRED PASIEKA/SCIENCE PHOTO LIBRARY/Getty

© ALFRED PASIEKA/SCIENCE PHOTO LIBRARY/Getty

Drug compounds that disrupt a key molecular interaction in the kidney could help patients with a rare condition in which excess fluids are excreted in the urine.

A team from Tokyo Medical and Dental University showed that preventing the tethering of binding proteins onto a critical signalling enzyme called protein kinase A (PKA) helps spur PKA into action. This in turn boosts the activity of the water channel protein that is otherwise defective in patients with nephrogenic diabetes insipidus, thereby promoting reabsorption of water in the kidney.

The researchers identified a class of drug compounds designed to break up this same interaction. In mouse models, these compounds enhanced PKA signalling and increased the ability of the kidney to concentrate urine.

The drugs may thus also help improve water balance in people with this kidney disorder.

Supported content

  1. Nature Communications 9, 1411 (2018). doi: 10.1038/s41467-018-03771-2
Institutions FC
Department of Nephrology, TMDU, Japan 0.64
Institute of Biomaterials and Bioengineering (IBB), TMDU, Japan 0.18
Division of Pediatrics, TMPU, Japan 0.09
School of Medicine, Nihon University, Japan 0.09

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