Functional and molecular characterization of a peptide transporter in the rat PC12 neuroendocrine cell line.
We have studied functional properties of peptide transport in the pheochromocytoma neuroendocrine cell line from rat. The neutral peptide D-Phe-L-Ala (resistant to hydrolysis) is a good substrate for uptake into these cells. Transport is substantially inhibited by diethylpyrocarbonate pretreatment and is stimulated by external acidification. It is sodium-independent and, unexpectedly, insensitive to membrane potential. Peptide uptake is inhibited by a wide variety of other di- and tripeptides but not by amino acids. The neuropeptide kyotorphin (opioid dipeptide (L-Tyr-L-Arg)) inhibits uptake of labelled peptide and trans-stimulates efflux showing that it is a transported substrate. These findings are discussed in relation to the molecular basis and physiological role of this transport system.
Hussain
I
I
Department of Human Anatomy and Genetics, University of Oxford, UK. imran.hussain@anat.ox.ac.uk
Zanic-Grubisic
T
T
Kudo
Y
Y
Boyd
C A
CA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D004151:Dipeptides / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D016716:PC12 Cells; D000074011:Peptide Transporter 1; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004151:Dipeptides; D004723:Endorphins; D009842:Oligopeptides; D000074011:Peptide Transporter 1; C489940:Slc15a1 protein, rat; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2; C019448:kyotorphin; C039552:phenylalanylalanine; D004047:Diethyl Pyrocarbonate