Mu and delta opioid receptor activation inhibits omega-conotoxin-sensitive calcium channels in a voltage- and time-dependent mode in the human neuroblastoma cell line SH-SY5Y.
Ca2+ channel modulation by the mu opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAGO) and the delta opiate agonists [d-Pen2, d-Pen5]-enkephalin (DPDPE) and [d-Ala2, d-Leu5]-enkephalin (DADLE) in cultured human neuroblastoma SH-SY5Y cells was investigated using the whole-cell variant of the patch-clamp technique. In SH-SY5Y cells, differentiated in vitro with retinoic acid, all agonists reversibly decreased high-voltage-activated, omega-conotoxin-sensitive Ba2+ currents in a concentration-dependent way. Inhibition was maximal with a 1 microM concentration of opiate agonists (76% with DAGO and 63% with delta agonists, when measured at 0 mV) and was characterized by a clear slow down of Ba2+ current activation at low test potentials. Both inhibition and slow down of activation were attenuated at more positive potentials, and could be partially relieved by strong conditioning depolarizations. 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 cells that were maximally activated by DAGO, suggesting that a common mechanism, involving the same type of modulating molecule, is responsible for Ca2+ channel inhibition promoted by activation of mu and delta opioid receptors in SH-SY5Y cells.
Toselli
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Istituto di Fisiologia Generale, Universita' di Pavia, Via Forlanini 6, I-27100, Pavia, Italy.
Tosetti
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Taglietti
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D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001464:Barium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-