Multiple actions of SC 38249: the blocker of both voltage-operated and second messenger-operated Ca2+ channels also inhibits Ca2+ extrusion.
((+-)-1,-2,3-bis-[(4-Methoxyphenyl)-methoxy]propyl)-1H-imidazole (SC 38249) and its 4-methoxyphenetyl analogue (SKF 96365) have been recently reported to block not only voltage-operated Ca2+ channels, but also the channels (second messenger-operated) that open after receptor activation of polyphosphoinositide hydrolysis in smooth muscle fibers and platelets. Fura-2 fluorescence studies in cerebellar neurons, glial and PC12 cells confirmed these effects of SC38249 and in addition demonstrated that the drug causes an inhibition of Ca2+ extrusion, presumably via the Ca2+ ATPase. This effect was particularly evident when [Ca2+]i was increased, regardless of treatment (glutamate or ionomycin). In contrast, the NMDA receptor channel activated by glutamate was not affected by SC 38249.
Ciardo
A
A
CNR Center of Cytopharmacology, San Raffaele Scientific Institute, University of Milano, Italy.
Meldolesi
J
J
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D016257:Fura-2; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001572:Benzofurans; D015220:Calcium Channels; D007093:Imidazoles; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C053318:1-(2,3-bis((4-methoxyphenyl)methoxy)propyl)-1H-imidazole; D013930:Thromboxane-A Synthase; D000252:Calcium-Transporting ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; D016257:Fura-2