MU-OPIOID AND DELTA-OPIOID RECEPTOR ACTIVATION INHIBITS OMEGA-CONOTOXIN-SENSITIVE CALCIUM CHANNELS IN A VOLTAGE-DEPENDENT AND TIME-DEPENDENT MODE IN THE HUMAN NEUROBLASTOMA CELL-LINE SH-SY5Y

Ca2+ channel modulation by the mu opioid agonist [D-Ala(2), N-Me-Phe(4 ), Gly(5)-ol]-enkephalin (DAGO) and the delta opiate agonists [D-Pen(2 ), D-Pens]-enkephalin (DPDPE) and [D-Ala(2), D-Leu(5)]-enkephalin (DAD LE) in cultured human neuroblastoma SH-SY5Y cells was investigated usi ng the whole-cell variant of the patch-clamp technique. In SH-SY5Y cel ls, differentiated in vitro with retinoic acid, all agonists reversibl y decreased high-voltage-activated, omega-conotoxin-sensitive Ba2+ cur rents in a concentration-dependent way. Inhibition was maximal with a 1 mu M concentration of opiate agonists (76% with DAGO and 63% with de lta agonists, when measured at 0 mV) and was characterized by a clear slow down of Ba2+ current activation at low test potentials. Both inhi bition and slow down of activation were attenuated at more positive po tentials, and could be partially relieved by strong conditioning depol arizations. Current suppression operated by both mu and delta agonists was prevented by pre-treatment of the cells with pertussis toxin. No sign of additivity was observed when delta agonists were applied to ce lls that were maximally activated by DAGO, suggesting that a common me chanism, involving the same type of modulating molecule, is responsibl e for Ca2+ channel inhibition promoted by activation of mu and delta o pioid receptors in SH-SY5Y cells.