Constitutive nitric oxide differentially regulates Na-H and Na-glucose cotransport in intestinal epithelial cells

被引:12
作者
Coon, Steven [1 ]
Kekuda, Ramesh [1 ]
Saha, Prosenjit [1 ]
Talukder, Jamilur R. [1 ]
Sundaram, Uma [1 ]
机构
[1] W Virginia Univ, Sch Med, Sect Digest Dis, Dept Med,Med Ctr, Morgantown, WV 26506 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2008年 / 294卷 / 06期
关键词
glucose absorption; regulation of transport; NHE3; SGLT1; Na absorption;
D O I
10.1152/ajpgi.00063.2008
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Previous in vivo studies suggest that constitutive nitric oxide (cNO) can regulate Na- glucose cotransport (SGLT1) and Na-H exchange (NHE3) in rabbit intestinal villus cells. Whether these two primary Na absorbing pathways are directly regulated by cNO and the mechanisms of this regulation in the enterocyte is not known. Thus nontransformed rat small intestinal epithelial cells (IEC-18) were treated with N-G-nitro-L-arginine methyl ester (L-NAME), which directly decreased cNO in these cells. L-NAME treatment decreased SGLT1 in IEC-18 cells. Kinetic studies demonstrated that the mechanism of inhibition was secondary to a decrease in the affinity of the cotransporter for glucose without a change in the number of cotransporters. In contrast, L-NAME treatment increased NHE3 in IEC-18 cells. Kinetic studies demonstrated that the mechanism of stimulation was by increasing the number of the exchangers without a change in the affinity for Na. Quantitative RT-PCR (RTQ-PCR) and Western blot analysis of SGLT1 demonstrated no change in mRNA and protein, respectively. RTQ-PCR and Western blot analysis of NHE3 indicated that NHE3 was increased by L-NAME treatment by an increase in mRNA and protein, respectively. These results indicate that decreased cNO levels directly mediate the inhibition of SGLT1 and stimulation of NHE3 in intestinal epithelial cells. Thus cNO directly but uniquely regulates the two primary Na- absorptive pathways in the mammalian small intestine.
引用
收藏
页码:G1369 / G1375
页数:7
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