TY - JOUR
T1 - Functional Identification of a Novel Transport System for Endogenous and Synthetic Opioid Peptides in the Rabbit Conjunctival Epithelial Cell Line CJVE
AU - Ananth, Sudha
AU - Karunakaran, Senthil
AU - Martin, Pamela M.
AU - Nagineni, Chandrasekharam N.
AU - Hooks, John J.
AU - Smith, Sylvia B.
AU - Prasad, Puttur D.
AU - Ganapathy, Vadivel
N1 - Funding Information:
This work was supported by the National Institutes of Health grant DA 21560.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Conjunctival epithelial cell
KW - Non-peptide opioid antagonists
KW - Opioid peptides
KW - Organic anion transporting polypeptides
KW - Transport process
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U2 - 10.1007/s11095-008-9709-x
DO - 10.1007/s11095-008-9709-x
M3 - Article
C2 - 18781380
AN - SCOPUS:63949085436
SN - 0724-8741
VL - 26
SP - 1226
EP - 1235
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 5
ER -