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 pheochrom ocytoma 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 a nd is stimulated by external acidification. It is sodium-independent and, u nexpectedly, 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 o f labelled peptide and trans-stimulates efflux showing that it is a transpo rted substrate. These findings are discussed in relation to the molecular b asis and physiological role of this transport system. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.