Insulin activates epithelial sodium channel (ENaC) via phosphoinositide 3-kinase in mammalian taste receptor cells

被引:32
作者
Baquero, Arian F. [1 ]
Gilbertson, Timothy A.
机构
[1] Utah State Univ, Dept Biol, Logan, UT 84322 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2011年 / 300卷 / 04期
基金
美国国家卫生研究院;
关键词
salt intake; GLUCOCORTICOID-REGULATED KINASE; NA+ CHANNEL; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; 3-OH KINASE; A6; CELLS; TRANSPORT; AMILORIDE; RAT; MICE; SGK1;
D O I
10.1152/ajpcell.00318.2010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Baquero AF, Gilbertson TA. Insulin activates epithelial sodium channel (ENaC) via phosphoinositide 3-kinase in mammalian taste receptor cells. Am J Physiol Cell Physiol 300: C860-C871, 2011. First published November 24, 2010; doi:10.1152/ajpcell.00318.2010.-Diabetes is a profound disease that results in a severe lack of regulation of systemic salt and water balance. From our earlier work on the endocrine regulation of salt taste at the level of the epithelial sodium channel (ENaC), we have begun to investigate the ability of insulin to alter ENaC function with patch-clamp recording on isolated mouse taste receptor cells (TRCs). In fungiform and vallate TRCs that exhibit functional ENaC currents (e. g., amiloride-sensitive Na+ influx), insulin (5-20 nM) caused a significant increase in Na+ influx at -80 mV (EC50 = 7.53 nM). The insulin-enhanced currents were inhibited by amiloride (30 mu M). Similarly, in ratiometric Na+ imaging using SBFI, insulin treatment (20 nM) enhanced Na+ movement in TRCs, consistent with its action in electrophysiological assays. The ability of insulin to regulate ENaC function is dependent on the enzyme phosphoinositide 3-kinase since treatment with the inhibitor LY294002 (10 mu M) abolished insulin-induced changes in ENaC. To test the role of insulin in the regulation of salt taste, we have characterized behavioral responses to NaCl using a mouse model of acute hyperinsulinemia. Insulin-treated mice show significant avoidance of NaCl at lower concentrations than the control group. Interestingly, these differences between groups were abolished when amiloride (100 mu M) was added into NaCl solutions, suggesting that insulin was regulating ENaC. Our results are consistent with a role for insulin in maintaining functional expression of ENaC in mouse TRCs.
引用
收藏
页码:C860 / C871
页数:12
相关论文
共 51 条
[1]   Pharmacology of phosphoinositides, regulators of multiple cellular functions [J].
Balla, T .
CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (06) :475-507
[2]   MEMBRANE CURRENTS IN TASTE CELLS OF THE RAT FUNGIFORM PAPILLA - EVIDENCE FOR 2 TYPES OF CA CURRENTS AND INHIBITION OF K-CURRENTS BY SACCHARIN [J].
BEHE, P ;
DESIMONE, JA ;
AVENET, P ;
LINDEMANN, B .
JOURNAL OF GENERAL PHYSIOLOGY, 1990, 96 (05) :1061-1084
[3]   Real-time three-dimensional imaging of lipid signal transduction:: apical membrane insertion of epithelial Na+ channels [J].
Blazer-Yost, BL ;
Vahle, JC ;
Byars, JM ;
Bacallao, RL .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 287 (06) :C1569-C1576
[4]   The cells and peripheral representation of sodium taste in mice [J].
Chandrashekar, Jayaram ;
Kuhn, Christina ;
Oka, Yuki ;
Yarmolinsky, David A. ;
Hummler, Edith ;
Ryba, Nicholas J. P. ;
Zuker, Charles S. .
NATURE, 2010, 464 (7286) :297-U182
[5]   Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na+ channel cell surface expression [J].
Debonneville, C ;
Flores, SY ;
Kamynina, E ;
Plant, PJ ;
Tauxe, C ;
Thomas, MA ;
Münster, C ;
Chraïbi, A ;
Pratt, JH ;
Horisberger, JD ;
Pearce, D ;
Loffing, J ;
Staub, O .
EMBO JOURNAL, 2001, 20 (24) :7052-7059
[6]   Distribution and characterization of functional amiloride-sensitive sodium channels in rat tongue [J].
Doolin, RE ;
Gilbertson, TA .
JOURNAL OF GENERAL PHYSIOLOGY, 1996, 107 (04) :545-554
[7]   The effect of amiloride on operantly conditioned performance in an NaCl taste detection task and NaCl preference in C57BL/6J mice [J].
Eylam, S ;
Spector, AC .
BEHAVIORAL NEUROSCIENCE, 2002, 116 (01) :149-159
[8]   sgk:: an essential convergence point for peptide and steroid hormone regulation of ENaC-mediated Na+ transport [J].
Faletti, CJ ;
Perrotti, N ;
Taylor, SI ;
Blazer-Yost, BL .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2002, 282 (03) :C494-C500
[9]   Epithelial Na+ channel activation and processing in mice lacking SGK1 [J].
Fejes-Toth, Geza ;
Frindt, Gustavo ;
Naray-Fejes-Toth, Aniko ;
Palmer, Lawrence G. .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2008, 294 (06) :F1298-F1305
[10]   The molecular physiology of taste transduction [J].
Gilbertson, TA ;
Damak, S ;
Margolskee, RF .
CURRENT OPINION IN NEUROBIOLOGY, 2000, 10 (04) :519-527