Abstract
Orphanin FQ, also known as nociceptin (NC),is a well-known ligand for opioid receptor-like ORLI receptor. This heptadecapeptide was identified as potently inhibiting the uptake of rat dopamine transporter (rDAT) which is stably expressed in CHO cells (designated D8 cells). Further kinetic analysis proved that this occurs through competitive inhibition with an IC50 of about 1.9 microM. Orphanin FQ also inhibits [3H]dopamine uptake by rat striatal synaptosomes, which confirmed the effect of orphanin FQ on D8 cells. Orphanin FQ was also found to inhibit GABA transporter type I (GATI) but not the serotonin transporter. These results suggest that orphanin FQ is an endogenous antagonist of dopamine transport and that it affects locomotion and other activities at least partly by inhibiting dopamine transporter and directly affecting dopamine transmission or by inhibiting GABA transporter to indirectly change dopaimne transmission.
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