NPC 15199

NPC 15199 is an anti-inflammatory agent.NPC-15199 [ (N- (9-fluorenylmethoxycarbonyl) L-leucine) ], a novel anti-inflammatory agent, increases intracellular Ca2+ concentration ([Ca2+]i) in human bladder female transitional cancer (BFTC) cells. Using fura-2 as a Ca2+ probe, NPC-15199 (0.1-2 mM) was found to increase [Ca2+]i concentration-dependently. The response saturated at 2-5 mM NPC-15199. The [Ca2+]i increase comprised an initial rise, a slow decay, and a plateau. Ca2+ removal partly inhibited the Ca2+ signals. In Ca2+-free medium, pretreatment with 1 mM NPC-15199 abolished the [Ca2+]i increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) ; and after pretreatment with thapsigargin, NPC-15199-induced Ca2+ release was dramatically inhibited. This indicates that NPC-15199 released internal Ca2+ mostly from the endoplasmic reticulum. Adding 3 mM Ca2+ increased [Ca2+]i in cells pretreated with 1 mM NPC-15199 in Ca2+-free medium. Together, the findings suggest that in BFTC bladder cancer cells, NPC-15199 induced Ca2+ release from the endoplasmic reticulum and activating Ca2+ entry.