Weihrauch Dirk, Kanchanapoo Jainuch, Ao Mei, Prasad Roli, Piyachaturawat Pawinee, Rao Mrinalini C
Department of Physiology and Biophysics, University of Illinois, Chicago, Illinois 60612, USA.
Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G439-50. doi: 10.1152/ajpgi.00163.2005. Epub 2005 Sep 15.
Intestinal handling of bile acids is age dependent; adult, but not newborn, ileum absorbs bile acids, and adult, but not weanling or newborn, distal colon secretes Cl(-) in response to bile acids. Bile acid transport involving the apical Na(+)-dependent bile acid transporter (Asbt) and lipid-binding protein (LBP) is well characterized in the ileum, but little is known about colonic bile acid transport. We investigated colonic bile acid transport and the nature of the underlying transporters and receptors. Colon from adult, weanling, and newborn rabbits was screened by semiquantitative RT-PCR for Asbt, its truncated variant t-Asbt, LBP, multidrug resistance-associated protein 3, organic solute transporter-alpha, and farnesoid X receptor. Asbt and LBP showed maximal expression in weanling and significantly less expression in adult and newborn rabbits. The ileum, but not the colon, expressed t-Asbt. Asbt, LBP, and farnesoid X receptor mRNA expression in weanling colon parallel the profile in adult ileum, a tissue designed for high bile acid absorption. To examine their functional role, transepithelial [(3)H]taurocholate transport was measured in weanling and adult colon and ileum. Under short-circuit conditions, weanling colon and ileum and adult ileum showed net bile acid absorption: 1.23 +/- 0.62, 5.53 +/- 1.20, and 11.41 +/- 3.45 nmol x cm(-2) x h(-1), respectively. However, adult colon secreted bile acids (-1.39 +/- 0.47 nmol x cm(-2) x h(-1)). We demonstrate for the first time that weanling, but not adult, distal colon shows net bile acid absorption. Thus increased expression of Asbt and LBP in weanling colon, which is associated with parallel increases in taurocholate absorption, has relevance in enterohepatic conservation of bile acids when ileal bile acid recycling is not fully developed.
肠道对胆汁酸的处理具有年龄依赖性;成年回肠能吸收胆汁酸,而新生回肠则不能,并且成年远端结肠会对胆汁酸做出反应分泌氯离子,而断奶期或新生期的远端结肠则不会。涉及顶端钠依赖性胆汁酸转运体(Asbt)和脂质结合蛋白(LBP)的胆汁酸转运在回肠中已有充分研究,但结肠胆汁酸转运的情况却知之甚少。我们研究了结肠胆汁酸转运以及相关转运体和受体的性质。通过半定量逆转录聚合酶链反应(RT-PCR)对成年、断奶期和新生兔的结肠进行筛查,检测Asbt、其截短变体t-Asbt、LBP、多药耐药相关蛋白3、有机溶质转运体α和法尼醇X受体。Asbt和LBP在断奶期兔结肠中的表达最高,在成年和新生兔结肠中的表达则显著较低。t-Asbt仅在回肠而非结肠中表达。断奶期结肠中Asbt、LBP和法尼醇X受体的mRNA表达情况与成年回肠(一种专为高效吸收胆汁酸而设计的组织)中的表达模式相似。为了研究它们的功能作用,我们测量了断奶期和成年结肠及回肠的跨上皮[³H]牛磺胆酸盐转运。在短路条件下,断奶期结肠和回肠以及成年回肠均表现出胆汁酸的净吸收:分别为每平方厘米每小时1.23±0.62、5.53±1.20和11.41±3.45纳摩尔。然而,成年结肠却分泌胆汁酸(每平方厘米每小时-1.39±0.47纳摩尔)。我们首次证明,断奶期而非成年期远端结肠表现出胆汁酸的净吸收。因此,断奶期结肠中Asbt和LBP表达的增加与牛磺胆酸盐吸收的相应增加相关,这在回肠胆汁酸循环尚未充分发育时,对胆汁酸的肠肝循环保存具有重要意义。