A Novel Perspective and Approach to Intestinal Octreotide Absorption: Sinomenine-Mediated Reversible Tight Junction Opening and Its Molecular Mechanism

International Journal of Molecular Sciences

Yuling Li¹  Zhijun Duan¹  Yan Tian²  Zhen Liu¹ 

[1] Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; E-Mails:;College of Pharmacy, Dalian Medical University, Dalian 116011, China; E-Mail:

关键词: octreotide;    sinomenine;    intestinal absorption;    tight junction;   

DOI  :  10.3390/ijms140612873

来源: mdpi

【 摘 要 】

In this work, we assessed the effects of sinomenine (SN) on intestinal octreotide (OCT) absorption both in Caco-2 cell monolayers and in rats. We also investigated the molecular mechanisms of tight junction (TJ) disruption and recovery by SN-mediated changes in the claudin-1 and protein kinase C (PKC) signaling pathway. The data showed that exposure to SN resulted in a significant decrease in the expression of claudin-1, which represented TJ weakening and paracellular permeability enhancement. Then, the recovery of TJ after SN removal required an increase in claudin-1, which demonstrated the transient and reversible opening for TJ. Meanwhile, the SN-mediated translocation of PKC-α from the cytosol to the membrane was found to prove PKC activation. Finally, SN significantly improved the absolute OCT bioavailability in rats and the transport rate in Caco-2 cell monolayers. We conclude that SN has the ability to enhance intestinal OCT absorption and that these mechanisms are related at least in part to the important role of claudin-1 in SN-mediated, reversible TJ opening via PKC activation.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland