Kirchhoff Philipp, Dave Mital H, Remy Christine, Kosiek Ortrud, Busque Stephanie M, Dufner Matthias, Geibel John P, Verrey Francois, Wagner Carsten A
Institute of Physiology and Center for Integrative Human Physiology (CIHP), University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
Pflugers Arch. 2006 Mar;451(6):738-48. doi: 10.1007/s00424-005-1507-2. Epub 2005 Nov 25.
Gastric acid secretion is regulated by a variety of stimuli, in particular histamine and acetyl choline. In addition, dietary factors such as the acute intake of a protein-rich diet and the subsequent increase in serum amino acids can stimulate gastric acid secretion only through partially characterized pathways. Recently, we described in mouse stomach parietal cells the expression of the system L heteromeric amino acid transporter comprised of the LAT2-4F2hc dimer. Here we address the potential role of the system L amino acid transporter in gastric acid secretion by parietal cells in freshly isolated rat gastric glands. RT-PCR, western blotting and immunohistochemistry confirmed the expression of 4F2-LAT2 amino acid transporters in rat parietal cells. In addition, mRNA was detected for the B(0)AT1, ASCT2, and ATB(0+) amino acid transporters. Intracellular pH measurements in parietal cells showed histamine-induced and omeprazole-sensitive H+-extrusion which was enhanced by about 50% in the presence of glutamine or cysteine (1 mM), two substrates of system L amino acid transporters. BCH, a non-metabolizable substrate and a competitive inhibitor of system L amino acid transport, abolished the stimulation of acid secretion by glutamine or cysteine suggesting that this stimulation required the uptake of amino acids by system L. In the absence of histamine glutamine also stimulated H+-extrusion, whereas glutamate did not. Also, phenylalanine was effective in stimulating H+/K+-ATPase activity. Glutamine did not increase intracellular Ca2+ levels indicating that it did not act via the recently described amino acid modulated Ca2+-sensing receptor. These data suggest a novel role for heterodimeric amino acid transporters and may elucidate a pathway by which protein-rich diets stimulate gastric acid secretion.
胃酸分泌受多种刺激因素调节，尤其是组胺和乙酰胆碱。此外，饮食因素，如急性摄入富含蛋白质的饮食以及随后血清氨基酸水平的升高，只能通过部分特征明确的途径刺激胃酸分泌。最近，我们在小鼠胃壁细胞中描述了由LAT2-4F2hc二聚体组成的L系统异聚氨基酸转运体的表达。在此，我们探讨L系统氨基酸转运体在新鲜分离的大鼠胃腺壁细胞胃酸分泌中的潜在作用。逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫组织化学证实了大鼠壁细胞中4F2-LAT2氨基酸转运体的表达。此外，还检测到了B(0)AT1、ASCT2和ATB(0+)氨基酸转运体的信使核糖核酸（mRNA）。壁细胞内的pH测量显示，组胺诱导的、奥美拉唑敏感的氢离子（H+）外流在L系统氨基酸转运体的两种底物谷氨酰胺或半胱氨酸（1毫摩尔）存在的情况下增强了约50%。BCH是一种不可代谢的底物，也是L系统氨基酸转运的竞争性抑制剂，它消除了谷氨酰胺或半胱氨酸对胃酸分泌的刺激作用，这表明这种刺激需要L系统摄取氨基酸。在没有组胺的情况下，谷氨酰胺也能刺激H+外流，而谷氨酸则不能。此外，苯丙氨酸在刺激H+/K+-ATP酶活性方面也有效。谷氨酰胺不会增加细胞内钙离子（Ca2+）水平，这表明它不是通过最近描述的氨基酸调节的Ca2+传感受体起作用。这些数据表明异二聚体氨基酸转运体具有新的作用，并且可能阐明富含蛋白质的饮食刺激胃酸分泌的途径。
