ARACHIDONATE 5-LIPOXYGENASE AND ITS ACTIVATING PROTEIN - PROMINENT HIPPOCAMPAL EXPRESSION AND ROLE IN SOMATOSTATIN SIGNALING

5-Lipoxygenase-activating protein (FLAP) is an 18-kDa integral membran e protein required, in peripheral cells, for the activation of 5-lipox ygenase (5-LO) and for the resulting synthesis of leukotrienes from ar achidonic acid. In the brain, the leukotrienes have been implicated in several pathophysiological events and in the electrophysiological eff ect of somatostatin, yet the cellular origin and role of these messeng er molecules are still poorly understood. In the present study, we use d reverse transcriptase-polymerase chain reaction, in situ hybridizati on, and immunohistochemistry to demonstrate that 5-LO and FLAP are exp ressed in various regions of the rat brain, including hippocampus, cer ebellum, primary olfactory cortex, superficial neocortex, thalamus, hy pothalamus, and brainstem. Highest levels of expression were observed in cerebellum and hippocampus. In the latter we demonstrate the coloca lization of 5-LO and FLAP in CA1 pyramidal neurons. Moreover, electrop hysiological experiments show that selective inhibition of FLAP with t he compound MK-886 (0.25-1 mu M) prevents the somatostatin-induced aug mentation of the hippocampal K+ M-current. Our results provide necessa ry evidence for the presence and signaling role of 5-LO and FLAP in ce ntral neurons and strongly support their proposed participation in som atostatin-receptor transmembrane signaling.