MULTIPLE ACTIONS OF SC-38249 - THE BLOCKER OF BOTH VOLTAGE-OPERATED AND 2ND 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.