title: Effects of kappa- and mu-opioid receptor agonists on Ca2+ channels in neuroblastoma cells: involvement of the orphan opioid receptor.
abstract: The effects of micro-, delta- and kappa-opioid receptor agonists, and orphanin FQ/nociceptin (Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln), on K+-induced [Ca2+]i increase were examined in SK-N-SH cells. Exposure to K+ (50 mM) resulted in a [Ca2+]i rise, which was blocked (-85%) by furaldipine (1 microM) and increased (63%) by BayK 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-pyridine-5 -carboxylate) (0.5 microM), indicating the involvement of L-type Ca2+ channels. The kappa-opioid receptor agonists 3,4-dichloro-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U-50488H) (1-50 microM) and 5,7,8-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]benze neacetamide (U-69593) (25 microM), and the mu-opioid receptor agonist sufentanil (100 nM-3 microM) inhibited the amplitude of K+-induced [Ca2+]i increase. The agonist of the orphan opioid receptor, orphanin FQ/nociceptin (1 microM), induced dual excitatory and inhibitory effects on the depolarisation-induced Ca2+ influx. The effects of the opioid receptor agonists were not blocked by the kappa-opioid receptor antagonist nor-binaltorphimine (1 microM), only weakly prevented by naloxone (10-100 microM) and naltrexone (100 microM), and partially prevented by pertussis toxin (100 ng/ml, 24 h). The antagonist of the orphan opioid receptor, [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 (1 microM), prevented the inhibitory effect of U-50488H, sufentanil and orphanin FQ. The present study provides pharmacological evidence for the presence of L-type Ca2+ channels in SK-N-SH cells, that are modulated by opioids through orphan opioid receptor activation.
authors.affiliation: Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Cantabria, Santander, Spain. hurlem@medi.unican.es
authors.forename: M A
authors.initials: MA
authors.lastname: Hurlé
authors.forename: A
authors.initials: A
authors.lastname: Sánchez
authors.forename: J
authors.initials: J
authors.lastname: García-Sancho
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma; D018847:Opioid Peptides / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000097629:Nociceptin
chemical_list: D000701:Analgesics, Opioid; D020746:Calcium Channels, L-Type; D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D000097629:Nociceptin