Effects of kappa- and mu-opioid receptor agonists on Ca2+ channels in neuroblastoma cells: involvement of the orphan opioid receptor

The effects of mu- delta- and kappa-opioid receptor agonists, and orphanin FQ/nociceptin (Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Arg-Lys-Leu-Ala-Asn- Gln), on Ks-induced [Ca2+](i) increase were examined in SK-N-SH cells. Expo sure to K+ (50 mM) resulted in a [Ca2+](i) rise, which was blocked (- 85%) by furaldipine (1 mu M) and increased (63%) by BayK 8644 (methyl-1,4-dihydr o-2,6-dimethyl 3-nitro-4-(2-trifluorornethyl-phenyl)-pyridine-5-carboxylate ) (0.5 mu M), indicating the involvement of L-type Ca2+ channels. The K-opi oid receptor agonists 3,4-dichloro-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl ]benzeneacetamide (U-50388H)(1-50 mu M) and 5,7,8-N-Methyl-N-[7-(1 -pyrroli dinyl)-1-oxaspiro[3,5]dec-8-yl]benzenencetamide (U-69593) (25 mu M)? and th e CL-opioid receptor agonist sufentanil(100 nM-3 mu M) inhibited the amplit ude of K+-induced [Ca2+](i) increase. The agonist of the orphan opioid rece ptor, orphanin FQ/nociceptin (1 mu M), induced dual excitatory and inhibito ry effects on the depolarisation-induced Ca2+ influx. The effects of the op ioid receptor agonists were not blocked by the K-opioid receptor antagonist nor-binaltorphimine (1 mu M), only weakly prevented by naloxone (10-100 mu M) and naltrexone (100 mu M), and partially prevented by pertussis toxin ( 100 ng/ml, 24 h). The antagonist of the orphan opioid receptor, [Phe(1)Psi( CH2-NH)Gly(2)]nociceptin(1-13)NH2(1 mu M), prevented the inhibitory effect of U-50488H, sufentanil and orphanin FQ. The present study provides pharmac ological evidence for the presence of L-type Ca2+ channels in SK-N-SH cells , that are modulated by opioids through orphan opioid receptor activation. (C) 1999 Elsevier Science B.V. All rights reserved.