Novel acid fatty acid sensing mechanisms operate in enteroendocrine cells: Calcium release from intracellular stores by cytosolic fatty acid

Abstract

Fatty acids (FA) with at least 12 carbon atoms increase intracellular Ca²⁺ ([Ca²⁺]_i) to stimulate cholecystokinin (CCK) release from enteroendocrine cells (EEC). Using the murine EEC line STC-1, we investigated whether candidate intracellular pathways transduce the FA signal, or whether FA themselves act within the cell to release Ca²⁺ directly from the intracellular store. In STC-1 cells loaded with fura-2, short (3 minutes) exposure of C12 fatty acid, but not C8 or C10, induced a dose-dependent increase in [Ca²⁺]_i, in the presence or absence of extracellular Ca²⁺. Various signaling inhibitors, including IP₃ receptor antagonists, all failed to block FA-induced Ca²⁺ responses. In permeabilized STC-1 cells loaded with the lower affinity Ca²⁺ dye magfura-2, and permeabilized by Streptolysin O, again C12 but not C8 or C10, induced release of stored Ca²⁺ dose dependently. However, 30 minutes exposure to C12 induced a sustained elevation of [Ca²⁺]_i in the presence of extracellular Ca²⁺, but only a transient response in the absence of extracellular Ca²⁺. These results suggest that at least two FA sensing mechanisms operate in enteroendocrine cells: intracellularly, FA (C12) transiently induces Ca²⁺ release from intracellular Ca²⁺ stores. However, they also induce sustained Ca²⁺ entry from the extracellular medium to maintain an elevated [Ca²⁺]_i. [Jpn J Physiol 54 Suppl:S116 (2004)]