Lysophosphatidic acid stimulates cAMP accumulation and cAMP response element-binding protein phosphorylation in immortalized hippocampal progenitor cells.

cAMP response element-binding protein (CREB) has been known to play a pivotal role in neuronal differentiation and neuronal plasticity. Lysophosphatidic acid (LPA) was reported to activate CREB in Rat2 fibroblast cells. To study the roles of LPA in neuronal differentiation, we determined whether LPA activates CREB in H19-7, hippocampal progenitor cells. LPA induced three-fold increase in cAMP level in a pertussis toxin-independent manner. Moreover, LPA stimulated CREB phosphorylation, which was inhibited by not only H89 but also Rp-cAMP. In H19-7 cells, high-level expression of lpa1 and moderate-level expression of lpa4 were detected, whereas any detectible expression of lpa2 or lpa3 was not detected by reverse transcription polymerase chain reaction. Together, these data suggested that LPA potentiates cAMP accumulation through activating Gs, and thereby, LPA can stimulate cAMP-CREB signaling cascade.