Cross-talk between different intracellular signalling pathways in the rat hippocampus

Abstract The activation of α1-adrenergic receptors in rat hippocampal slices enhances polyphosphoinositide (PPI) breakdown and cyclicAMP (cAMP) accumulation. The latter effect is antagonized by different protein kinase C (PKC) inhibitors and mimicked by a diacylglycerol (DAG) analogue, 1,2-diolein, which activates PKC, suggesting that cAMP synthesis is indirectly affected by α1-adrenoceptors through the stimulated generation of DAG upon PPI hydrolysis. Furthermore the elevation of hippocampal cAMP decreases the ability of α1-receptor agonists to enhance PPI breakdown. It is proposed that the observed effects are part of a complex cross-talk between PPI and AC signalling pathways operating in hippocampal neurons.