Inhibition of the renal betaine transporter by calcium ions

American Journal of Physiology. Renal Physiology
Stephen A KempsonMichael Sturek

Abstract

Chronic upregulation of the renal betaine/GABA transporter (BGT1) by hypertonic stress has been well documented, but it is not known whether BGT1 can be regulated acutely after insertion in the basolateral plasma membrane. Related transporters, such as the rat brain GABA transporter, can be rapidly removed from the plasma membrane through activation of G protein-coupled receptors. The goal of the present study was to determine whether acute changes in extracellular and/or intracellular Ca(2+) will regulate BGT1 transport activity at the plasma membrane level in Madin-Darby canine kidney cells subjected to 24-h hypertonic stress. After brief pretreatment with a Ca(2+)-free solution, the addition of extracellular Ca(2+) in the transport assay produced dose-dependent inhibition of Na(+)-GABA cotransport. Maximum inhibition was 49% at 2 mM Ca(2+) (P < 0.05). Fura 2 imaging confirmed that addition of 2 mM Ca(2+) produced a transient increase in intracellular Ca(2+) that preceded transport inhibition. Acute inhibition of Na(+)-GABA cotransport was reproduced by addition of thapsigargin (5 microM) and ionomycin (10 microM). Amino acid transport system A, assayed as a control, was not inhibited. Brief treatment with phorbol esters repr...Continue Reading

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Citations

May 2, 2008·American Journal of Physiology. Renal Physiology·Stephen A KempsonMichael Sturek
Mar 13, 2012·Biochemical and Biophysical Research Communications·Zohreh HosseinzadehFlorian Lang
May 6, 2014·Frontiers in Physiology·Stephen A KempsonNiels C Danbolt
Feb 1, 2018·Urolithiasis·Ryan W WalkerKathleen S Hering-Smith
May 16, 2014·American Journal of Physiology. Renal Physiology·Eva S SchweikhardBirgitta C Burckhardt
Oct 12, 2007·Physiological Reviews·Maurice B BurgNatalia I Dmitrieva

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