Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki S-I, Kuwahara A
Laboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, Institute for Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan.
J Physiol Pharmacol. 2008 Aug;59 Suppl 2:251-62.
Short chain fatty acids (SCFAs) are the major anions in the large intestine. They are produced by a bacterial fermentation of dietary fiber. SCFAs are known to have a variety of physiological and pathphysiological effects on intestine. However, the mechanisms by which intraluminal SCFAs are sensed are not known. In 2003, two orphan G protein coupled receptors (GPRs), GPR41 and GPR43, have been cloned and demonstrated to be receptors for SCFAs. Thus, we had attempted to make antibodies raised against GPR43 and GPR41 to elucidate the roles of SCFAs on colonic functions. We have also evaluated the effects of SCFAs on colonic motility to define the physiological roles on luminal SCFAs. In rat and human colon, GPR43 protein was detected by Western blot analysis in extracts of whole wall and separated mucosa, but not in muscle plus submucosa extract. By immunohistochemistry, GPR43 immunoreactivity was localized with enteroendocrine cells expressing peptide YY, whereas 5-HT immunoreactive enteroendocrine cells were not immunoreactive for GPR43. GPR41 immunoreactivity was also found in human colon. In functional studies, propionate and butyrate concentration-dependently (10 microM - 10 mM) induced phasic and tonic contractions in rat colonic circular muscle. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT(4) receptor antagonists SB204070. However, acetate did not induce phasic or tonic contractions. Propionate-induced responses were not observed in mucosal free preparations. The present results suggest that the SCFA-induced physiological effects on colonic functions might be attributable to the activation of SCFA receptors on epithelial cells in the colon.
短链脂肪酸（SCFAs）是大肠中的主要阴离子。它们由膳食纤维的细菌发酵产生。已知SCFAs对肠道具有多种生理和病理生理作用。然而，肠腔内SCFAs的感知机制尚不清楚。2003年，两种孤儿G蛋白偶联受体（GPRs），即GPR41和GPR43，被克隆出来并被证明是SCFAs的受体。因此，我们试图制备针对GPR43和GPR41的抗体，以阐明SCFAs对结肠功能的作用。我们还评估了SCFAs对结肠运动的影响，以确定肠腔内SCFAs的生理作用。在大鼠和人类结肠中，通过蛋白质免疫印迹分析在全壁提取物和分离的黏膜中检测到GPR43蛋白，但在肌肉加黏膜下层提取物中未检测到。通过免疫组织化学，GPR43免疫反应性定位于表达肽YY的肠内分泌细胞，而5-羟色胺（5-HT）免疫反应性肠内分泌细胞对GPR43无免疫反应性。在人类结肠中也发现了GPR41免疫反应性。在功能研究中，丙酸盐和丁酸盐浓度依赖性地（10微摩尔 - 10毫摩尔）诱导大鼠结肠环行肌的相性和紧张性收缩。丙酸盐诱导的相性收缩被阿托品、河豚毒素和5-HT(4)受体拮抗剂SB204070减弱。然而，乙酸盐未诱导相性或紧张性收缩。在无黏膜的制剂中未观察到丙酸盐诱导的反应。目前的结果表明，SCFAs对结肠功能的生理作用可能归因于结肠上皮细胞上SCFA受体的激活。
