GLUTAMINE AND INTESTINAL TRANSPORT AND MUCOSAL GROWTH

轮状病毒腹泻，婴儿腹泻的主要原因，是由于 肠内转运受损，以未分化的 肠细胞 谷氨酰胺是肠道代谢的主要燃料， 肠上皮细胞因子和损伤后粘膜修复刺激因子。 我们 已经发现，L-谷氨酰胺促进中性NaCl的吸收， 和轮状病毒感染的仔猪空肠（可能通过偶联Na/H和 Cl/HCO 3交换）。 其他人发现L-谷氨酰胺增强肝细胞 通过刺激鸟氨酸脱羧酶（ODC）活性在培养物中生长。 此外，L-天冬酰胺，结构上类似于谷氨酰胺， ODC和跨膜Na/H交换（在肝癌细胞中），导致 胞质内碱化，细胞增殖的假定信号。 在肠细胞中，代谢燃料对细胞内pH（pHi）的影响 和多胺代谢尚未确定。 我们的研究将集中在谷氨酰胺刺激NaCl的机制 在未分化的上皮中吸收和细胞生长。 我们将使用 轮状病毒感染的猪空肠和分离的猪上皮细胞 单层（IPEC-J2）以模拟肠功能。 具体目标1评估 如果谷氨酰胺刺激偶联的跨膜Na/H和Cl/HCO 3交换， Na-K-2Cl共转运。 目标2研究了 谷氨酰胺、氧化代谢、细胞ATP储存和Na，K-ATP酶 活动 具体目标3确定谷氨酰胺及其 pHi代谢。 具体目标4旨在评估谷氨酰胺 刺激ODC并启动粘膜生长。 目标5确定， 谷氨酰胺促进病毒性肠炎的粘膜恢复。 我们的研究结果可以改善婴儿肠道疾病的口服治疗 损伤和腹泻。

Rotavirus diarrhea, the leading cause of infant diarrhea, is the result of impaired transport in an intestine dominated by undifferentiated enterocytes. Glutamine, the major intestinal metabolic fuel, is a growth factor for enterocytes and a stimulator of mucosal repair after damage. We have found that L-glutamine promotes neutral NaCl absorption across normal and rotavirus-infected piglet jejunum (probably via coupled Na/H and Cl/HCO3 exchanges). Others have found that L-glutamine enhances hepatocyte growth in culture by stimulating ornithine decarboxylase (ODC) activity. Furthermore, L-asparagine, structurally similar to glutamine, stimulates ODC and transmembrane Na/H exchange (in hepatoma cells), resulting in intracytoplasmic alkalinization, a putative signal for cell proliferation. In enterocytes, the effects of metabolic fuels on intracellular pH (pHi) and polyamine metabolism have not been determined. Our studies will focus on the mechanisms by which glutamine stimulates NaCl absorption and cell growth in an undifferentiated epithelium. We will use rotavirus-infected pig jejunum and isolated porcine epithelial cell monolayers (IPEC-J2) to model intestinal function. Specific Aim 1 assesses if glutamine stimulates coupled transmembrane Na/H and Cl/HCO3 exchanges or Na-K-2Cl cotransport. Objective 2 examines the relationship between glutamine, oxidative metabolism, cellular ATP stores, and Na, K-ATPase activity. Specific Aim 3 determines the effect of glutamine and its metabolism on pHi. Specific Aim 4 is designed to assess how glutamine stimulates ODC and initiates mucosal growth. Objective 5 determines if glutamine promotes mucosal recovery in viral enteritis. Our findings could improve the oral treatment of infants with intestinal damage and diarrhea.