Atrial natriuretic peptide is eliminated from the brain by natriuretic peptide receptor-C-mediated brain-to-blood efflux transport at the blood-brain barrier.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Shingo ItoTetsuya Terasaki

Abstract

Cerebral atrial natriuretic peptide (ANP), which is generated in the brain, has functions in the regulation of brain water and electrolyte balance, blood pressure and local cerebral blood flow, as well as in neuroendocrine functions. However, cerebral ANP clearance is still poorly understood. The purpose of this study was to clarify the mechanism of blood-brain barrier (BBB) efflux transport of ANP in mouse. Western blot analysis showed expression of natriuretic peptide receptor (Npr)-A and Npr-C in mouse brain capillaries. The brain efflux index (BEI) method confirmed elimination of [(125)I]human ANP (hANP) from mouse brain across the BBB. Inhibition studies suggested the involvement of Npr-C in vivo. Furthermore, rapid internalization of [(125)I]hANP by TM-BBB4 cells (an in vitro BBB model) was significantly inhibited by Npr-C inhibitors and by two different Npr-C-targeted short interfering RNAs (siRNAs). Finally, treatment with 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) significantly increased Npr-C expression in TM-BBB4 cells, as determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted absolute proteomics. Our results indicate that Npr-C mediates brain-to-blood efflux transport of ANP at the...Continue Reading

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Citations

Mar 25, 2014·Genetic Testing and Molecular Biomarkers·De-Guang XingYun-Jie Wang
May 28, 2016·Neuroscience and Biobehavioral Reviews·Simin MahinradBehnam Sabayan
Oct 23, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Isabelle F van der VelpenBehnam Sabayan
Apr 2, 2021·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Tetsuya Terasaki

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Methods Mentioned

BETA
protein assay
electrophoresis
transfection
PCR

Software Mentioned

MULTI
Analyst

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