title: Ruthenium red inhibits selectively chromaffin cell calcium channels.
abstract: The effect of Ruthenium red (RR) on ionic currents and catecholamine secretion was studied in chromaffin cells. This polycation inhibited 59 mM potassium-stimulated 45Ca2+ uptake in a concentration-dependent manner (IC50 = 5 +/- 0.2 microM). This effect was more evident at extracellular calcium concentrations over 1 mM and was not abolished by neuraminidase pretreatment. RR also inhibited potassium-stimulated catecholamine secretion (IC50 = 6 +/- 0.9 microM). These results were corroborated by patch-clamp in whole-cell recordings. RR inhibited chromaffin cell calcium currents (IC50 = 7 microM) without affecting significantly either sodium or potassium currents. Radioligand binding studies in adrenomedullary plasma membranes showed that RR inhibited [125I]omega-conotoxin GVIA binding but it had no effect on specific binding of [3H]nitrendipine. The effect of the RR on calcium currents was additive with the inhibitory effect observed with 10 microM nitrendipine. The residual dihydropyridine-resistant calcium current was inhibited with a potency similar to that determined under control conditions in the absence of nitrendipine. These results demonstrate that RR selectively inhibits calcium channels; however, this polycation was not selective for a particular calcium channel subtype.
authors.affiliation: Departamento de Neuroquímica, Facultad de Medicina-Instituto de Neurociencias, Universidad de Alicante, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gomis
authors.forename: L M
authors.initials: LM
authors.lastname: Gutierrez
authors.forename: F
authors.initials: F
authors.lastname: Sala
authors.forename: S
authors.initials: S
authors.lastname: Viniegra
authors.forename: J A
authors.initials: JA
authors.lastname: Reig
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D007457:Iodine Radioisotopes; D009568:Nitrendipine / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology*; D014316:Tritium; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007457:Iodine Radioisotopes; D010455:Peptides; D014316:Tritium; D012430:Ruthenium Red; C038806:1,4-dihydropyridine; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D009638:Norepinephrine