Characterization of the currents induced by sigma ligands in NCB20 neuroblastoma cells.
Electrical and pharmacological properties of currents induced by compounds having affinities for putative sigma receptors were investigated with NCB20 cells by use of the whole-cell patch-clamp technique. Antipsychotics and naloxone induced inward currents with a decrease in membrane conductance at a holding potential of -60 mV. The rank order of potency for compounds inducing these currents was bromperidol > haloperidol > mosapramine = clocapramine > carpipramine > chlorpromazine > remoxipride > naloxone. Sulpiride, which does not have affinity for sigma receptors, induced inward currents only slightly. Haloperidol-induced currents were not affected by the pretreatments with 10 microM of sulpiride, dopamine, atropine, N-methyl-D-aspartate, 2-amino-7-phosphonoheptanoic acid, morphine or A23187, 100 nM of ICS 205-930, 100 microM of forskolin, 1 microM of phorbol-12,13-dibutyrate, or 100 ng/ml of cholera or pertussis toxins. The reversal potential of the currents induced by haloperidol, naloxone or remoxipride was dependent on the concentration of external or internal potassium. These results indicate that the currents induced by the tested compounds are due to blockade of tonic, outward potassium currents and suggest that these agents act on putative sigma receptors and that the second messenger systems within the cell are not essential for the coupling between the receptors and the channels.
Morio
Y
Y
Research Laboratory, Yoshitomi Pharmaceutical Industries Ltd., Fukuoka, Japan.
Tanimoto
H
H
Yakushiji
T
T
Morimoto
Y
Y
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism*; D006224:Cricetinae; D004594:Electrophysiology; D006220:Haloperidol / Q000494:pharmacology; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D017480:Receptors, sigma / Q000187:drug effects*; D017330:Remoxipride / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D014150:Antipsychotic Agents; D008024:Ligands; D015221:Potassium Channels; D017480:Receptors, sigma; D017330:Remoxipride; D009270:Naloxone; D006220:Haloperidol