The human neuroblastoma cell line SH-SY5Y expresses the 'orphan' opioid receptor (ORLI). We have demonstrated that nociceptin, the putative endogenous ligand for ORLI, produces a concentrationdependent inhibition of the N-type calcium channel current in these cells (IC,0 42 nM). In addition, in the presence of carbachol, nociceptin increased the intracellular concentration of Ca2" (ECQ0 60 nM). Both effects of nociceptin were blocked by pertussis toxin pretreatment but not by the opioid antagonists CTAP (1 pM), naltrindole (1 gM) and naloxone (10 gM).