Yusuke Takizawa1, Ryoka Nakamura2, Takuro Kurita2, Takanori Nakajima2. 1. Division of Clinical Pharmaceutics, Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan. y-takizawa@nichiyaku.ac.jp. 2. Division of Clinical Pharmaceutics, Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
Abstract
BACKGROUND: The unstirred water layer (UWL) is an integral part of the apical surface of mucosal epithelia and comprises mucins (MUC), for which there are many molecular species. Galectins, a family of β-galactoside-binding lectins, form a lattice barrier on surface epithelial cells by interacting with MUC. Lactose inhibits the galectin-MUC interaction. Therefore, the present study investigated the galectin-MUC interaction in the mucosa of the gastrointestinal tract and its role in intestinal barrier functions. MATERIALS AND RESULTS: The effects of lactose hydrate (LH) on the membrane permeability of the rat small intestine and Caco-2 cells were examined. LH enhanced the membrane permeability of the rat small intestine, which contains the UWL, via a transcellular route, for which the UWL is the rate limiting factor. The membrane permeability of Caco-2 cells, in which the UWL is insufficient, was not affected by LH. The apparent permeability coefficient (Papp) of a paracellular marker was not significantly altered in the rat small intestine or Caco-2 cells treated with LH at any concentration. Furthermore, the Papp of β-naphthol which is a transcellular marker was not significantly altered in Caco-2 cells treated with LH, but was significantly increased in the rat small intestine in a LH concentration-dependent manner. CONCLUSIONS: The present results demonstrate that the physical barrier has an important function in gastrointestinal membrane permeability, and LH-induced changes increase the transcellular permeability of β-naphthol in rat small intestine.
BACKGROUND: The unstirred water layer (UWL) is an integral part of the apical surface of mucosal epithelia and comprises mucins (MUC), for which there are many molecular species. Galectins, a family of β-galactoside-binding lectins, form a lattice barrier on surface epithelial cells by interacting with MUC. Lactose inhibits the galectin-MUC interaction. Therefore, the present study investigated the galectin-MUC interaction in the mucosa of the gastrointestinal tract and its role in intestinal barrier functions. MATERIALS AND RESULTS: The effects of lactose hydrate (LH) on the membrane permeability of the rat small intestine and Caco-2 cells were examined. LH enhanced the membrane permeability of the rat small intestine, which contains the UWL, via a transcellular route, for which the UWL is the rate limiting factor. The membrane permeability of Caco-2 cells, in which the UWL is insufficient, was not affected by LH. The apparent permeability coefficient (Papp) of a paracellular marker was not significantly altered in the rat small intestine or Caco-2 cells treated with LH at any concentration. Furthermore, the Papp of β-naphthol which is a transcellular marker was not significantly altered in Caco-2 cells treated with LH, but was significantly increased in the rat small intestine in a LH concentration-dependent manner. CONCLUSIONS: The present results demonstrate that the physical barrier has an important function in gastrointestinal membrane permeability, and LH-induced changes increase the transcellular permeability of β-naphthol in rat small intestine.
Authors: Roberto Canaparo; Niklas Finnström; Loredana Serpe; Anna Nordmark; Elisabetta Muntoni; Mario Eandi; Anders Rane; Gian Paolo Zara Journal: Clin Exp Pharmacol Physiol Date: 2007-11 Impact factor: 2.557