Ruthenium red inhibits selectively chromaffin cell calcium channels.
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.
Gomis
A
A
Departamento de Neuroquímica, Facultad de Medicina-Instituto de Neurociencias, Universidad de Alicante, Spain.
Gutierrez
L M
LM
Sala
F
F
Viniegra
S
S
Reig
J A
JA
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
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