Skip to main content
Log in

Lactose hydrate can increase the transcellular permeability of β-naphthol in rat jejunum and ileum

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Childers NK, Bruce MG, McGhee JR (1989) Molecular mechanisms of immunoglobulin A defense. Annu Rev Microbiol 43:503–536

    Article  CAS  Google Scholar 

  2. Watanabe T, Maeda K, Nakai C, Sugiyama Y (2013) Investigation of the effect of the uneven distribution of CYP3A4 and P-glycoprotein in the intestine on the barrier function against xenobiotics: a simulation study. J Pharm Sci 102(9):3196–3204

    Article  CAS  Google Scholar 

  3. Suzuki H (1999) Analysis of xenobiotic detoxification system mediated by efflux transporters. Yakugaku Zasshi 119(11):822–834

    Article  CAS  Google Scholar 

  4. Lindner S, Halwachs S, Wassermann L, Honscha W (2013) Expression and subcellular localization of efflux transporter ABCG2/BCRP in important tissue barriers of lactating dairy cows, sheep and goats. J Vet Pharmacol Ther 36(6):562–570

    Article  CAS  Google Scholar 

  5. Canaparo R, Finnström N, Serpe L, Nordmark A, Muntoni E, Eandi M, Rane A, Zara GP (2007) Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum. Clin Exp Pharmacol Physiol 34(11):1138–1144

    CAS  PubMed  Google Scholar 

  6. Madara JL, Carlson S, Anderson JM (1993) ZO-1 maintains its spatial distribution but dissociates from junctional fibrils during tight junction regulation. Am J Physiol 264(5 Pt 1):C1096–C1101

    Article  CAS  Google Scholar 

  7. Chiou WL (1994) Effect of “unstirred” water layer in the intestine on the rate and extent of absorption after oral administration. Biopharm Drug Dispos 15(8):709–717

    Article  CAS  Google Scholar 

  8. Yonezawa S, Higashi M, Yamada N, Yokoyama S, Kitamoto S, Kitajima S, Goto M (2011) Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int 61(12):697–716

    Article  CAS  Google Scholar 

  9. Williams SJ, McGuckin MA, Gotley DC, Eyre HJ, Sutherland GR, Antalis TM (1999) Two novel mucin genes down-regulated in colorectal cancer identified by differential display. Cancer Res 59(16):4083–4089

    CAS  PubMed  Google Scholar 

  10. Kim YS, Ho SB (2010) Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep 12(5):319–330

    Article  Google Scholar 

  11. Cooper DN (2002) Galectinomics: finding themes in complexity. Biochim Biophys Acta 1572:209–231

    Article  CAS  Google Scholar 

  12. Boscher C, Dennis JW, Nabi IR (2011) Glycosylation, galectins and cellular signaling. Curr Opin Cell Biol 23:383–392

    Article  CAS  Google Scholar 

  13. Di Lella S, Sundblad V, Cerliani JP, Guardia CM, Estrin DA, Vasta GR, Rabinovich GA (2011) When galectins recognize glycans: from biochemistry to physiology and back again. Biochemistry 50:7842–7857

    Article  Google Scholar 

  14. Raz A, Carmi P, Raz T, Hogan V, Mohamed A, Wolman SR (1991) Molecular cloning and chromosomal mapping of a human galactoside-binding protein. Cancer Res 51:2173–2178

    CAS  PubMed  Google Scholar 

  15. Ochieng J, Plait D, Tail L, Hogan V, Raz T, Carmi P, Raz A (1993) Structure-function relationship of a recombinant human galactoside-binding protein. Biochemistry 32:4455–4460

    Article  CAS  Google Scholar 

  16. Argüeso P, Guzman-Aranguez A, Mantelli F, Cao Z, Ricciuto J, Panjwani N (2009) Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier. J Biol Chem 284(34):23037–23045

    Article  Google Scholar 

  17. Bojić-Trbojević Z, Jovanović Krivokuća M, Kolundžić N, Petronijević M, Vrzić-Petronijević S, Golubović S, Vićovac L (2014) Galectin-1 binds mucin in human trophoblast. Histochem Cell Biol 142(5):541–5318

    Article  Google Scholar 

  18. Tamura M, Tanaka T, Fujii N, Tanikawa T, Oka S, Takeuchi T, Hatanaka T, Kishimoto S, Arata Y (2020) Potential interaction between galectin-2 and MUC5AC in mouse gastric mucus. Biol Pharm Bull 43:356–360

    Article  CAS  Google Scholar 

  19. Takizawa Y, Kishimoto H, Nakagawa M, Sakamoto N, Tobe Y, Furuya T, Tomita M, Hayashi M (2013) Effects of pharmaceutical excipients on membrane permeability in rat small intestine. Int J Pharm 453:363–370

    Article  CAS  Google Scholar 

  20. Takizawa Y, Tobe Y, Sakamoto N, Sakamoto J, Hayashi M (2020) Sodium nitroprusside enhances absorption in the rat jejunum via the transcellular route. J Membr Biol 253(3):221–228

    Article  CAS  Google Scholar 

  21. Leffer H (1997) Introduction to galectins. Trends Glycosci Glycotechnol 9(45):9–19

    Article  Google Scholar 

  22. Tamura M, Sato D, Nakajima M, Saito M, Sasaki T, Tanaka T, Hatanaka T, Takeuchi T, Arata Y (2017) Identification of galectin-2-mucin interaction and possible formation of a high molecular weight lattice. Biol Pharm Bull 40:1789–1795

    Article  CAS  Google Scholar 

  23. Takizawa Y, Aizawa Y, Furuya T, Hayashi M (2019) Influence of pharmaceutical excipients on membrane transport via transcellular route in rat small intestine. Sch Acad J Pharm 8(11):488–496

    CAS  Google Scholar 

  24. Takizawa Y, Furuno Y, Hayashi M (2021) Effects of polyvinylpyrrolidone (K90) on membrane permeation via the transcellular route in the rat jejunum. J Pharm Investig 51(3):311–316

    Article  CAS  Google Scholar 

  25. Takizawa Y, Goto N, Furuya T, Hayashi M (2020) Influence of pharmaceutical excipients on membrane transport of P-glycoprotein substrate in rat small intestine. Eur J Drug Metab Pharmacokinet 45(5):645–652

    Article  CAS  Google Scholar 

  26. Yamagata T, Kusuhara H, Morishita M, Takayama K, Benameur H, Sugiyama Y (2007) Effect of excipients on breast cancer resistance protein substrate uptake activity. J Control Release 124:1–5

    Article  CAS  Google Scholar 

  27. Yamagata T, Kusuhara H, Morishita M, Takayama K, Benameur H, Sugiyama Y (2009) Characterization of the inhibition of breast cancer resistance protein-mediated efflux of mitoxantrone by pharmaceutical excipients. Int J Pharm 370:216–219

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Mr. Masaya Uno, Mr. Junya Oguri, Mr. Naruya Kunii, and Miss Koume Yoda for their technical assistance.

Funding

The present study was supported in part by a grant from the Toyo Institute of Food Technology.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yusuke Takizawa.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

All animal experiments were performed according to the guidelines of Nihon Pharmaceutical University. The present study was approved by the Nihon Pharmaceutical University Committee on the Care and Use of Laboratory Animals (approval number: AE2021-001).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 107 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takizawa, Y., Nakamura, R., Kurita, T. et al. Lactose hydrate can increase the transcellular permeability of β-naphthol in rat jejunum and ileum. Mol Biol Rep 49, 8685–8692 (2022). https://doi.org/10.1007/s11033-022-07709-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07709-2

Keywords

Navigation