Bombesin-like peptides stimulate phosphatidylinositol turnover in rat brain slices

The ability of bombesin (BN)-like peptides to stimulate phosphatidylinositol turnover in rat brain slices was investigated. BN (1 microM) significantly stimulated inositol-1-phosphate (IP1) but not inositol-4,5-biphosphate (IP2) or inositol-1,4,5-trisphosphate (IP3) production using frontal cortex slices in the presence of LiCl (7.5 mM); BN had no effect on cAMP or cGMP levels. BN and the structurally-related gastrin releasing peptide (GRP) elevated IP1 levels in a dose-dependent manner. Similarly, nanomolar concentrations of the GRP fragment (Ac-GRP20-27) significantly elevated IP1 levels, whereas micromolar concentrations of the inactive GRP1-16 did not. BN significantly elevated IP1 levels in those brain regions enriched in BN receptors such as the olfactory bulb, hippocampus, striatum, thalamus and frontal cortex, whereas IP1 levels were not significantly increased in areas which have a low density of BN receptors such as the cerebellum, medulla/pons and midbrain. These data suggest that CNS BN receptors may utilize phosphatidylinositol as a second messenger.