Activation of mg2+/ca2+-sensing inhibits hormone-stimulated mg2+
uptake in mouse distal convoluted tubule cells.
Bapty, Brian W., Long-Jun Dai, Gordon Ritchie, Lucie Canaff, Geoffrey
N. Hendy, and Gary A. Quamme.
Department of Medicine, University of British Columbia, University
Hospital, Koerner Pavilion, Vancouver, BC Canada and Departments of
Medicine, Physiology and Human Genetics, McGill University and Royal
Victoria Hospital, Montreal, Quebec, Canada
APStracts 5:0103F, 1998.
The distal convoluted tubule plays a significant role in renal
magnesium conservation. An immortalized mouse distal convoluted
tubule (MDCT) cell line has been extensively used to study the
cellular mechanisms of magnesium transport in this nephron segment.
MDCT cells possess an extracellular polyvalent cation-sensing
mechanism responsive to Mg2+, Ca2+, and neomycin. The present studies
determined the effect of Mg2+/Ca2+-sensing on hormone-mediated cAMP
formation and Mg2+ uptake in MDCT cells. MDCT cells were Mg2+
-depleted by culturing in Mg2+-free media for 16 hr and Mg2+ uptake
was measured by microfluorescence after placing the depleted cells in
1.5 mM MgCl2. The mean rate of Mg2+ uptake, d([Mg2+]i)/dt, was 164+/
-5 nM/s in control MDCT cells. Activation of Mg2+/Ca2+-sensing with
neomycin did not affect basal Mg2+ uptake, 155+/-5 nM/s. We have
previously reported that treatment of MDCT cells with either glucagon
or arginine vasopressin stimulated Mg2+ entry. In the present
studies, the addition of extracellular Mg2+ or Ca2+ inhibited
glucagon- and AVP-stimulated cAMP formation and Mg2+ uptake in
concentration-dependent manner with half-maximal concentrations of
about 1.5 and 3.0 mM, respectively. Exogenous cAMP or forskolin
stimulated Mg2+ uptake in the presence of Mg2+/Ca2+-sensing
activation. We infer from these studies that Mg2+/Ca2+-sensing
mechanisms located in the distal convoluted tubule, may play a role
in control of distal magnesium absorption.
Received 2 December 1997; accepted in final form 21 May 1998.
APS Manuscript Number F379-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 16 June 1998