Halldén G, Aponte G W
Department of Nutritional Sciences, University of California, Berkeley, California 94720-3104, USA.
J Biol Chem. 1997 May 9;272(19):12591-600. doi: 10.1074/jbc.272.19.12591.
Peptide tyrosine tyrosine (PYY) is a gut hormone present in endocrine cells in the lower intestine that can be released by the presence of luminal free fatty acids (FFAs). The biological action of this peptide includes inhibition of gut motility and gastrointestinal and pancreatic secretions. Intestinal fatty acid-binding protein (I-FABP) binds FFA and may be involved in their cytosolic trafficking. Quantitative in situ hybridization on heterogeneous populations of small intestinal somatic cell hybrids selected for endogenous I-FABP expression (hBRIE 380i cells) demonstrated a 5-fold increase in I-FABP transcripts in response to PYY (within 6 h) that was confined to clusters of differentiated cells, whereas ribonuclease protection assays performed on heterogeneous populations of these cells showed no significant differences. High affinity PYY receptors, with an IC50 of 5-50 pM, were identified in both differentiated and nondifferentiated cell populations, as determined by competitive binding assays and autoradiography. In situ hybridization of rat ileal tissue also revealed differing patterns of mRNA expression for liver fatty acid-binding protein (L-FABP) and I-FABP. Only I-FABP mRNA was detected in the villus tips. This localization correlated with the expression pattern of I-FABP mRNA in the hBRIE 380i cells where changes in transcripts were observed only in differentiated cells that did not incorporate bromodeoxyuridine. The sustained expression of I-FABP transcripts in the villar tips suggests (unlike L-FABP) that older terminally differentiated cell populations of the mucosa can still be PYY responsive. These studies demonstrate that physiological concentrations of PYY can regulate I-FABP and place this peptide in a key position as part of a feedback system that determines the processing of cytosolic FFA in the enterocyte. In addition, these studies suggest a mechanism whereby luminal agents can modulate expression of proteins in terminally differentiated cells in the gastrointestinal mucosa.
肽酪氨酰酪氨酸（PYY）是一种存在于下肠道内分泌细胞中的肠道激素，可由腔内游离脂肪酸（FFA）的存在而释放。这种肽的生物学作用包括抑制肠道蠕动以及胃肠和胰腺分泌。肠脂肪酸结合蛋白（I-FABP）结合FFA，并可能参与其胞质运输。对选择用于内源性I-FABP表达的小肠体细胞杂种异质群体（hBRIE 380i细胞）进行的定量原位杂交显示，响应PYY（6小时内）时，I-FABP转录本增加了5倍，且仅限于分化细胞簇，而对这些细胞的异质群体进行的核糖核酸酶保护试验未显示出显著差异。通过竞争性结合试验和放射自显影测定，在分化和未分化细胞群体中均鉴定出高亲和力的PYY受体，其IC50为5 - 50 pM。大鼠回肠组织的原位杂交还揭示了肝脂肪酸结合蛋白（L-FABP）和I-FABP的mRNA表达模式不同。仅在绒毛尖端检测到I-FABP mRNA。这种定位与hBRIE 380i细胞中I-FABP mRNA的表达模式相关，在该细胞中，仅在未掺入溴脱氧尿苷的分化细胞中观察到转录本的变化。绒毛尖端I-FABP转录本的持续表达表明（与L-FABP不同），黏膜中较老的终末分化细胞群体仍可对PYY产生反应。这些研究表明，生理浓度的PYY可调节I-FABP，并使该肽在作为决定肠细胞胞质FFA加工的反馈系统的一部分中处于关键位置。此外，这些研究提示了一种腔内因子可调节胃肠道黏膜终末分化细胞中蛋白质表达的机制。
