The transport and efflux of glycosylated luteinising hormone-releasing hormone analogues in Caco-2 cell model: contributions of glucose transporters and efflux systems

Moradi, Shayli Varasteh, Varamini, Pegah and Toth, Istvan (2014) The transport and efflux of glycosylated luteinising hormone-releasing hormone analogues in Caco-2 cell model: contributions of glucose transporters and efflux systems. Journal of Pharmaceutical Sciences, Early View . doi:10.1002/jps.24120

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Author Moradi, Shayli Varasteh
Varamini, Pegah
Toth, Istvan
Title The transport and efflux of glycosylated luteinising hormone-releasing hormone analogues in Caco-2 cell model: contributions of glucose transporters and efflux systems
Journal name Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0022-3549
1520-6017
Publication date 2014-08-29
Year available 2014
Sub-type Article (original research)
DOI 10.1002/jps.24120
Open Access Status
Volume Early View
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2015
Language eng
Formatted abstract
Luteinising hormone-releasing hormone (LHRH) analogues have wide therapeutic applications in the treatment of prostate cancers and endocrine disorders. The structure of LHRH was modified using a glycosylation strategy to increase the permeability of the peptide across biological membranes. Lactose, galactose and glucose units were coupled to LHRH peptide, and the impact of glucose transporters, GLUT2 and SGLT1, was investigated in the transport of the analogues. Results showed the contribution of both transporters in the transport of all LHRH analogues. In the presence of glucose transporter inhibitors, reduction in the apparent permeability (Papp) was greatest for compound 6, which contains a glucose unit in the middle of the sequence (Papp = 58.54 ± 4.72 cm/s decreased to Papp = 1.6 ± 0.345 cm/s). The basolateral to apical flux of the glycosylated derivatives and the impact of two efflux pumps was also examined in Caco-2 cell monolayers. The efflux ratios (ERs) of all LHRH analogues in Caco-2 cells were in the range of 0.06–0.2 except for compound 4 (galactose modified, ER = 8.03). We demonstrated that the transport of the glycosylated peptides was facilitated through glucose transporters. The proportion of glucose and lactose derivatives pumped out by efflux pumps did not affect the Papp values of the analogues.
Keyword LHRH
SGLT1
GLUT2
Transport
Caco-2 cell
Peptides
MRP2
P-glycoprotein
Glycosylation
Efflux pumps
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 29 AUG 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
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Created: Fri, 19 Sep 2014, 12:40:56 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences