Caffeine-induced telencephalic vesicle evagination in early post-implantation mouse embryos involves cAMP-dependent protein kinase (PKA) inhibition

Other studies have shown that caffeine accelerates telencephalic vesicle ev agination in early post-implantation mouse embryos. The present study exami nes the effect of caffeine on gene modulation in post-implantation mouse em bryos. Using mRNA differential display, we observed that caffeine increased gene expression of the regulatory subunit (RI alpha) of cAMP-dependent pro tein kinase (PKA). RT-PCR analysis confirmed an increase in expression of t his gene in caffeine-exposed embryos when compared with saline-treated cont rols. Using a fluorescent substrate of PKA, we found that PKA activity in t he presence of cAMP was lower in caffeine-treated embryos than in controls. Treatment with H89 and PKI(12-24)amide, two inhibitors of PKA activity, mi micked the effects of caffeine on telencephalic vesicle formation. Together these data suggest that in early post-implantation mouse embryos caffeine modulates gene expression of the RI alpha subunit of PKA and that caffeine- induced inhibition of PKA activity plays a role in early telencephalic evag ination.