Abstract
We have recently identified a Na+/Cl - coupled transport system in mammalian cells for endogenous and synthetic opioid peptides. This transport system does not transport dipeptides/ tripeptides, but is stimulated by these small peptides. Here we investigated the influence of L-kyotorphin (L-Tyr-L-Arg), an endogenous dipeptide with opioid activity, on this transport system. The activity of the transport system, measured in SK-N-SH cells (a human neuronal cell line) with deltorphin II as a model substrate, was stimulated ∼2.5-fold by L-kyotorphin, with half-maximal stimulation occurring at∼100 μM. The stimulation was associated primarily with an increase in the affinity for deltorphin II. The stimulation caused by L-kyotorphin was stereospecific; L-Tyr-D-Arg (D-kyotorphin) had minimal effect. The influence of L-kyotorphin was observed also in a different cell line which expressed the opioid peptide transport system. While L-kyotorphin is a stimulator of opioid peptide transport, it is a transportable substrate for the H+-coupled peptide transporter PEPT2, which is expressed widely in the brain. Since the activity of the opioid peptide transport system is modulated by extracellular L-kyotorphin and since PEPT2 is an important determinant of extracellular Lkyotorphin in the brain, the expression/activity of PEPT2 may be a critical factor in the modulation of opioidergic neurotransmission in vivo.
Original language | English (US) |
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Pages (from-to) | 254-262 |
Number of pages | 9 |
Journal | Drug Metabolism and Pharmacokinetics |
Volume | 23 |
Issue number | 4 |
DOIs | |
State | Published - 2008 |
Keywords
- Kyotorphin
- Opioid peptide transport
- Opioidergic neurotransmission
- PEPT2
- SK-N-SH cell line
- Stereospecificity
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Pharmacology (medical)