Orphanin FQ: an endogenous antagonist of rat brain dopamine transporter

Orphanin FQ, also known as nociceptin (NC), is a well-known ligand for opio id receptor-like ORLI receptor. This heptadecapeptide was identified as pot ently inhibiting the uptake of rat dopamine transporter (rDAT) which is sta bly expressed in CHO cells (designated D8 cells). Further kinetic analysis proved that this occurs through competitive inhibition with an IC50 of abou t 1.9 muM. Orphanin FQ also inhibits [H-3]dopamine uptake by rat striatal s ynaptosomes, which confirmed the effect of orphanin FQ on D8 cells. Orphani n FQ was also found to inhibit GABA transporter type I (GATI) but not the s erotonin transporter. These results suggest that orphanin FQ is an endogeno us antagonist of dopamine transport and that it affects locomotion and othe r activities at least partly by inhibiting dopamine transporter and directl y affecting dopamine transmission or by inhibiting GABA transporter to indi rectly change dopamine transmission. NeuroReport 12:699-702 (C) 2001 Lippin cott Williams & Wilkins.