TY - JOUR
T1 - Differential modulation of sodium- and chloride-dependent opioid peptide transport system by small nonopioid peptides and free amino acids
AU - Miyauchi, Seiji
AU - Gopal, Elangovan
AU - Thakkar, Santosh V.
AU - Ichikawa, Satoshi
AU - Prasad, Puttur D.
AU - Ganapathy, Vadivel
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/4
Y1 - 2007/4
N2 - We recently identified a novel opioid peptide transport system in the retinal pigment epithelium that transports opioid peptides by a Na +/Cl--dependent process. Here we describe a similar transport system expressed in SK-N-SH cells (a human neuronal cell line) and show for the first time that the activity of the transport system is modulated differentially by lysine and small nonopioid peptides. The transport process in SK-N-SH cells, monitored with deltorphin II as the substrate, is Na +/Cl--dependent and interacts with several opioid peptides, consisting of 5 to 13 amino acids. The activity of this transport system is markedly stimulated by specific dipeptides and tripeptides, with significant stimulation observable at low micromolar concentrations. The ion dependence, Na+/Cl--activation kinetics, and opioid peptide selectivity of the transport system, however, remain unchanged. The stimulation by the modulatory peptides is associated with an increase in maximal velocity with no change in substrate affinity of the system. Amino acids have no or little effect on the transport system, with the exception of lysine. This cationic amino acid inhibits the transport system, with significant inhibition occurring at physiologic concentrations of the amino acid. The inhibitory effect is primarily associated with a decrease in the maximal velocity of the transport system with little change in substrate affinity. Methyl and ethyl esters of lysine retain the inhibitory potency, but most other structural analogs have no effect. The differential modulation of the transport system by lysine and specific small peptides has important implications in the biology and pharmacology of opioid peptides.
AB - We recently identified a novel opioid peptide transport system in the retinal pigment epithelium that transports opioid peptides by a Na +/Cl--dependent process. Here we describe a similar transport system expressed in SK-N-SH cells (a human neuronal cell line) and show for the first time that the activity of the transport system is modulated differentially by lysine and small nonopioid peptides. The transport process in SK-N-SH cells, monitored with deltorphin II as the substrate, is Na +/Cl--dependent and interacts with several opioid peptides, consisting of 5 to 13 amino acids. The activity of this transport system is markedly stimulated by specific dipeptides and tripeptides, with significant stimulation observable at low micromolar concentrations. The ion dependence, Na+/Cl--activation kinetics, and opioid peptide selectivity of the transport system, however, remain unchanged. The stimulation by the modulatory peptides is associated with an increase in maximal velocity with no change in substrate affinity of the system. Amino acids have no or little effect on the transport system, with the exception of lysine. This cationic amino acid inhibits the transport system, with significant inhibition occurring at physiologic concentrations of the amino acid. The inhibitory effect is primarily associated with a decrease in the maximal velocity of the transport system with little change in substrate affinity. Methyl and ethyl esters of lysine retain the inhibitory potency, but most other structural analogs have no effect. The differential modulation of the transport system by lysine and specific small peptides has important implications in the biology and pharmacology of opioid peptides.
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U2 - 10.1124/jpet.106.116806
DO - 10.1124/jpet.106.116806
M3 - Article
C2 - 17259448
AN - SCOPUS:33947360597
SN - 0022-3565
VL - 321
SP - 257
EP - 264
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -