Ca2+-channel blockers modulate the oxidative burst induced with arachidonic acid in macrophage-like P 388D1 cells. Interaction with peripheral benzodiazepines.
Ca2+-channel blockers are shown to modulate, like peripheral benzodiazepines, the oxidative burst induced by arachidonic acid in the macrophage-like P 388D1 cell line. Nifedipine (1 and 10 nM) enhanced the cellular response to arachidonate; this stimulation by nifedipine was reversed by PK 1195, a specific antagonist for the peripheral benzodiazepine binding site. Verapamil (5 microM), on the other hand, antagonized the stimulation of the oxidative burst by benzodiazepines. The data suggest some possible interaction of Ca2+-channel blockers at the benzodiazepine binding site or at a secondary step in the activation mechanism. None of the molecules modulated the calcium influx triggered by arachidonate. Instead, the oxidative response of P 388D1 cells to arachidonate was inhibited by K+-channel blockers, quinidine and tetraethylammonium bromide.
Zavala
F
F
Institut de Chimie des Substances Naturelles, C.N.R.S., Gif-sur-Yvette, France.
Lenfant
M
M
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007941:Leukemia P388 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D013481:Superoxides / Q000378:metabolism
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013481:Superoxides; D001569:Benzodiazepines; D016718:Arachidonic Acid