GLUTAMINE AND INTESTINAL TRANSPORT AND MUCOSAL GROWTH

轮状病毒腹泻是婴儿腹泻的主要原因，是由 以未分化为主的肠道转运受损 肠道细胞。谷氨酰胺，主要的肠道代谢燃料，是一种生长 肠细胞因子和损伤后粘膜修复的刺激因子。我们 研究发现，L-谷氨酰胺促进中性氯化钠的吸收 和轮状病毒感染的仔猪空肠(可能通过偶联Na/H和 Cl2/HCO3交换)。其他人发现L-谷氨酰胺能增强肝细胞 通过刺激鸟氨酸脱羧酶(ODC)活性在培养中生长。 此外，L-天冬酰胺在结构上与谷氨酰胺相似，可刺激 ODC和跨膜Na/H交换(在肝癌细胞中)，导致 胞质内碱化，可能是细胞增殖的信号。 在肠细胞中，代谢燃料对细胞内pH(Phi)的影响 多胺代谢尚未确定。 我们的研究将集中在谷氨酰胺刺激氯化钠的机制上 未分化上皮中的吸收和细胞生长。我们将使用 轮状病毒感染猪空肠和分离的猪上皮细胞 单分子层(IPEC-J2)来模拟肠功能。特定目标1评估 如果谷氨酰胺刺激耦合的跨膜Na/H和Cl/HCO3交换或 Na-K-2Cl共转运。目标2考察了 谷氨酰胺、氧化代谢、细胞ATP储存和Na，K-ATPase 活动。特异靶3确定谷氨酰胺及其受体的作用 Phi上的代谢。具体目标4旨在评估谷氨酰胺如何 刺激ODC，启动粘膜生长。目标5确定是否 谷氨酰胺可促进病毒性肠炎的粘膜恢复。 我们的研究结果可以改善婴幼儿肠道疾病的治疗。 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.