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Mucins are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine.
Pharm Res. 2019 Sep 16; 36(11):162.PR

Abstract

PURPOSE

Mucins are the principal glycoproteins in mucus and have been implicated in the limitation of intestinal drug absorption; however, the contribution of these molecules to intestinal drug absorption remains unclear. In this study, the relationship between the effect of the mucus layer on intestinal drug permeation and mucin distribution in different parts of the rat gastrointestinal tract was evaluated.

METHODS

The intestinal permeability of various lipophilic drugs in rat small intestine was evaluated using the in vitro sac method. The expression profiles of mucin mRNA and proteins were evaluated by quantitative real-time RT-PCR and western blotting, respectively.

RESULTS

The intestinal permeability of griseofulvin and antipyrine was enhanced by dithiothreitol (DTT) treatment in the proximal small intestine, such as duodenum and jejunum, but not in the distal regions. The mRNA expression analysis of rat mucin genes revealed that the intestinal expression of Muc5ac was considerably higher in the duodenum, whereas that of Muc1, Muc2, and Muc3A was gradually increased toward the lower intestine. In addition, Muc5ac protein was detected only in the luminal fluids from the proximal small intestine after DTT treatment.

CONCLUSIONS

Mucus limits the intestinal permeation of lipophilic drugs in the rat proximal small intestine, in which Muc5ac may be involved.

Authors+Show Affiliations

Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo, 192-0392, Japan. kinoue@toyaku.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31529336

Citation

Miyazaki, Kaori, et al. "Mucins Are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine." Pharmaceutical Research, vol. 36, no. 11, 2019, p. 162.
Miyazaki K, Kishimoto H, Muratani M, et al. Mucins are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine. Pharm Res. 2019;36(11):162.
Miyazaki, K., Kishimoto, H., Muratani, M., Kobayashi, H., Shirasaka, Y., & Inoue, K. (2019). Mucins are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine. Pharmaceutical Research, 36(11), 162. https://doi.org/10.1007/s11095-019-2701-9
Miyazaki K, et al. Mucins Are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine. Pharm Res. 2019 Sep 16;36(11):162. PubMed PMID: 31529336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mucins are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine. AU - Miyazaki,Kaori, AU - Kishimoto,Hisanao, AU - Muratani,Miho, AU - Kobayashi,Hanai, AU - Shirasaka,Yoshiyuki, AU - Inoue,Katsuhisa, Y1 - 2019/09/16/ PY - 2019/06/08/received PY - 2019/09/06/accepted PY - 2019/9/19/entrez PY - 2019/9/19/pubmed PY - 2019/12/4/medline KW - Muc5ac KW - mucin KW - mucus layer KW - passive diffusion SP - 162 EP - 162 JF - Pharmaceutical research JO - Pharm Res VL - 36 IS - 11 N2 - PURPOSE: Mucins are the principal glycoproteins in mucus and have been implicated in the limitation of intestinal drug absorption; however, the contribution of these molecules to intestinal drug absorption remains unclear. In this study, the relationship between the effect of the mucus layer on intestinal drug permeation and mucin distribution in different parts of the rat gastrointestinal tract was evaluated. METHODS: The intestinal permeability of various lipophilic drugs in rat small intestine was evaluated using the in vitro sac method. The expression profiles of mucin mRNA and proteins were evaluated by quantitative real-time RT-PCR and western blotting, respectively. RESULTS: The intestinal permeability of griseofulvin and antipyrine was enhanced by dithiothreitol (DTT) treatment in the proximal small intestine, such as duodenum and jejunum, but not in the distal regions. The mRNA expression analysis of rat mucin genes revealed that the intestinal expression of Muc5ac was considerably higher in the duodenum, whereas that of Muc1, Muc2, and Muc3A was gradually increased toward the lower intestine. In addition, Muc5ac protein was detected only in the luminal fluids from the proximal small intestine after DTT treatment. CONCLUSIONS: Mucus limits the intestinal permeation of lipophilic drugs in the rat proximal small intestine, in which Muc5ac may be involved. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/31529336/Mucins_are_Involved_in_the_Intestinal_Permeation_of_Lipophilic_Drugs_in_the_Proximal_Region_of_Rat_Small_Intestine_ L2 - https://doi.org/10.1007/s11095-019-2701-9 DB - PRIME DP - Unbound Medicine ER -