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Functional Identification of a Novel Transport System for Endogenous and Synthetic Opioid Peptides in the Rabbit Conjunctival Epithelial Cell Line CJVE

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Abstract

Purpose

To investigate whether conjunctival epithelial cells express transport processes for opioid peptides.

Methods

We monitored the uptake of [3H]deltorphin II and [3H]DADLE, two hydrolysis-resistant synthetic opioid peptides, in the rabbit conjunctival epithelial cell line CJVE and elucidated the characteristics of the uptake process.

Results

CJVE cells express robust uptake activity for deltorphin II and DADLE. Both opioid peptides compete with each other for transport. Several endogenous and synthetic opioid peptides, but not non-peptide opioid antagonists, are recognized by the transport process. Though various peptides inhibit the uptake of deltorphin II and DADLE in a similar manner, the uptake of deltorphin II is partly Na+-dependent whereas that of DADLE mostly Na+-independent. The transport process shows high affinity for many endogenous/synthetic opioid peptides. Functional features reveal that this transport process may be distinct from the opioid peptide transport system described in the retinal pigment epithelial cell line ARPE-19 and also from the organic anion transporting polypeptides, which are known to transport opioid peptides.

Conclusions

CJVE cells express a novel, hitherto unknown transport process for endogenous/synthetic opioid peptides. This new transport process may offer an effective delivery route for opioid peptide drugs to the posterior segment of the eye.

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Acknowledgements

This work was supported by the National Institutes of Health grant DA 21560.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia, 30912, USA

    Sudha Ananth, Senthil Karunakaran, Pamela M. Martin, Puttur D. Prasad & Vadivel Ganapathy

  2. Laboratory of Immunology, National Eye Institute, Bethesda, Maryland, 20892, USA

    Chandrasekharam N. Nagineni & John J. Hooks

  3. Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia, 30912, USA

    Sylvia B. Smith & Vadivel Ganapathy

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  1. Sudha Ananth
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  2. Senthil Karunakaran
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  3. Pamela M. Martin
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  4. Chandrasekharam N. Nagineni
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  8. Vadivel Ganapathy
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Correspondence to Vadivel Ganapathy.

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Ananth, S., Karunakaran, S., Martin, P.M. et al. Functional Identification of a Novel Transport System for Endogenous and Synthetic Opioid Peptides in the Rabbit Conjunctival Epithelial Cell Line CJVE. Pharm Res 26, 1226–1235 (2009). https://doi.org/10.1007/s11095-008-9709-x

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  • DOI: https://doi.org/10.1007/s11095-008-9709-x

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