Sgambati S A, Turowski G A, Basson M D
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, and the VA Connecticut Health Care System, West Haven, USA.
J Gastrointest Surg. 1997 Nov-Dec;1(6):561-8. doi: 10.1016/s1091-255x(97)80073-x.
Peptide YY (PYY) is produced by colonic mucosal endocrine cells and modulates gastrointestinal endocrine activity through specific Y-receptors. The direct effects of PYY on intestinal mucosal growth and differentiation remain uncharacterized. The abundance of PYY in colonic mucosa suggests that PYY acts locally to maintain colonocytic differentiation. We tested this hypothesis in human Caco-2 intestinal epithelial cells, which express alkaline phosphatase (AP) and dipeptidyl dipeptidase (DP), brush-border enzymes differentially concentrated in large and small intestinal mucosa, respectively. The effects of PYY on enzyme specific activity were compared with those of pancreatic polypeptide, neuropeptide-Y, vasoactive intestinal peptide, pentagastrin, bombesin, and selective Y1- and Y2-receptor agonists. Brush-border enzyme activity was assessed by AP and DP specific activity in cell lysates quantitated spectrophotometrically following synthetic substrate digestion. PYY, neuropeptide-Y, pancreatic polypeptide, and vasoactive intestinal peptide (10(-7) mol/L) stimulated AP activity. PYY brought about the greatest increase (38.0%+/-11.0%, n=48). Only PYY decreased DP specific activity (7.9%+/-2.2%, n=48). The Y2-agonist but not the Y1-agonist mimicked these PYY effects (increasing AP 28.3%+/-3.5% and decreasing DP 10.4%+/-3.6%). These data suggest that PYY promotes differentiation toward a colonocytic phenotype in Caco-2 intestinal epithelial cells and that this effect may be mediated through the Y2-receptor subtype.
肽YY（PYY）由结肠黏膜内分泌细胞产生，并通过特定的Y受体调节胃肠内分泌活动。PYY对肠黏膜生长和分化的直接作用仍未明确。结肠黏膜中PYY的丰富表明PYY在局部发挥作用以维持结肠细胞的分化。我们在人Caco-2肠上皮细胞中验证了这一假设，该细胞表达碱性磷酸酶（AP）和二肽基肽酶（DP），这两种刷状缘酶分别在小肠和大肠黏膜中差异浓缩。将PYY对酶比活性的影响与胰多肽、神经肽Y、血管活性肠肽、五肽胃泌素、蛙皮素以及选择性Y1和Y2受体激动剂的影响进行比较。在合成底物消化后，通过分光光度法定量测定细胞裂解物中的AP和DP比活性来评估刷状缘酶活性。PYY、神经肽Y、胰多肽和血管活性肠肽（10^(-7) mol/L）刺激了AP活性。PYY引起的增加最大（38.0%±11.0%，n = 48）。只有PYY降低了DP比活性（7.9%±2.2%，n = 48）。Y2激动剂而非Y1激动剂模拟了这些PYY效应（AP增加28.3%±3.5%，DP降低10.4%±3.6%）。这些数据表明，PYY促进Caco-2肠上皮细胞向结肠细胞表型分化，且这种作用可能通过Y2受体亚型介导。
