Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle

Détails

Ressource 1Télécharger: Blanchard Paracellin-1 Mg Ca reabsorption human TALH Kidney Int 2001.pdf (555.50 [Ko])
Etat: Public
Version: de l'auteur
Licence: Non spécifiée
ID Serval
serval:BIB_8B36EC3732C8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle
Périodique
Kidney International
Auteur(s)
Blanchard A., Jeunemaitre X., Coudol P., Dechaux M., Froissart M., May A., Demontis R., Fournier A., Paillard M., Houillier P.
ISSN
0085-2538
Statut éditorial
Publié
Date de publication
2001
Volume
59
Numéro
6
Pages
2206-15
Langue
anglais
Notes
Blanchard, A
Jeunemaitre, X
Coudol, P
Dechaux, M
Froissart, M
May, A
Demontis, R
Fournier, A
Paillard, M
Houillier, P
eng
Research Support, Non-U.S. Gov't
2001/06/16 10:00
Kidney Int. 2001 Jun;59(6):2206-15.
Résumé
BACKGROUND: A new protein, named paracellin 1 (PCLN-1), expressed in human thick ascending limb (TAL) tight junctions, possibly plays a critical role in the control of magnesium and calcium reabsorption, since mutations of PCLN-1 are present in the hypomagnesemia hypercalciuria syndrome (HHS). However, no functional experiments have demonstrated that TAL magnesium and calcium reabsorption were actually impaired in patients with HHS. METHODS: Genetic studies were performed in the kindred of two unrelated patients with HHS. Renal magnesium and calcium reabsorption in TAL were analyzed in one homozygous affected patient of each family, one patient with extrarenal hypomagnesemia (ERH), and two control subjects (CSs). RESULTS: We found two yet undescribed mutations of PCLN-1 (Gly 162 Val, Ala 139 Val). In patients with HHS, renal magnesium and calcium reabsorptions were impaired as expected; NaCl renal conservation during NaCl deprivation and NaCl tubular reabsorption in diluting segment were intact. Furosemide infusion in CS markedly increased NaCl, Mg, and Ca urinary excretion rates. In HHS patients, furosemide similarly increased NaCl excretion, but failed to increase Mg and Ca excretion. Acute MgCl(2) infusion in CS and ERH patient provoked a dramatic increase in urinary calcium excretion without change in NaCl excretion. When combined with MgCl(2) infusion, furosemide infusion remained able to induce normal natriuretic response, but was unable to increase urinary magnesium and calcium excretion further. In HHS patients, calciuric response to MgCl(2) infusion was blunted. CONCLUSION: This study is the first to our knowledge to demonstrate that homozygous mutations of PCLN-1 result in a selective defect in paracellular Mg and Ca reabsorption in the TAL, with intact NaCl reabsorption ability at this site. In addition, the study supports a selective physiological effect of basolateral Mg(2+) and Ca(2+) concentration on TAL divalent cation paracellular permeability, that is, PCLN-1 activity.
Mots-clé
Adolescent, Adult, Calcium/*metabolism, Cations, Divalent/metabolism, Child, Claudins, Diuretics, Family Health, Female, Furosemide, Genotype, Homozygote, Humans, Loop of Henle/*metabolism, Magnesium Chloride/*pharmacokinetics, Male, Membrane Proteins/*genetics/*metabolism, Middle Aged, Natriuresis/drug effects/physiology, Nephrocalcinosis/diagnosis/*genetics/metabolism, Pedigree, Phenotype, Point Mutation, Sodium Chloride/metabolism
Open Access
Oui
Création de la notice
03/03/2016 17:49
Dernière modification de la notice
20/08/2019 15:49
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