GEA 857 blocks potassium channels in the membrane and, thereby, prolongs muscarinic cholinergic responses in N1E-115 neuroblastoma cells.
GEA 857 [2-(4-chlorophenyl)-1,1-dimethylethyl 2-amino-3-methylbutanoate], a structural analogue of the serotonin (5-HT) uptake inhibitor alaprocalate but without effects on the 5-HT uptake, was shown to potentiate muscarinic cholinergic responses in N1E-115 neuroblastoma cells. In intracellular recording experiments, GEA 857 (1 microM) increased the cell input resistance and prolonged the action potential. It also prolonged the cellular response to carbachol acting on muscarinic receptors in a manner mimicked by potassium channel blockers such as 4-aminopyridine and TEA. GEA 857 did not affect the carbachol stimulated uptake of 45Ca, but depressed the carbachol activated outflow of 86Rb from neuroblastoma cells. The conclusion drawn from these results is that GEA 857 reduces potassium conductances in the membrane in N1E-115 neuroblastoma cells and, thereby, prolongs muscarinic agonist-induced responses.
Hedlund
B
B
Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
Ogren
S O
SO
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy*; D015221:Potassium Channels / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D015221:Potassium Channels; D011976:Receptors, Muscarinic; C077603:GEA 857; D002217:Carbachol; D014633:Valine; D012413:Rubidium; D002118:Calcium