The human neuroblastoma cell line SH-SY5Y expresses the 'orphan' opioid receptor (ORL1). We have demonstrated that nociceptin, the putative endogenous ligand for ORL1, produces a concentration-dependent inhibition of the N-type calcium channel current in these cells (IC50 42 nM). In addition, in the presence of carbachol, nociceptin increased the intracellular concentration of Ca2+ (EC(50) 60 nM). Both effects of nociceptin were blocked by pertussis toxin pretreatment but not by the opioid antagonists CTAP (1 mu M), naltrindole (1 mu M) and naloxone (10 mu M).