Although it has been shown that Epac1
mRNA is expressed ubiquitously and Epac2
mRNA predominantly in the brain and endocrine tissues, developmental and pathophysiological changes of these molecules have not been characterized. Developmental changes were analyzed in murine heart, brain, kidneys, and lungs by RT-PCR analysis, which revealed more drastic developmental changes of Epac2
mRNA than Epac1. Only the Epac2
mRNA in kidney showed a transient expression pattern with dramatic decline into adulthood. In addition to developmental changes, we found that
Epac gene expression was upregulated in myocardial
hypertrophy induced by chronic
isoproterenol infusion or pressure overload by transverse aortic banding. Both Epac1 and Epac2
mRNA were upregulated in
isoproterenol-induced
left ventricular hypertrophy, whereas only Epac1 was increased in pressure overload-induced
hypertrophy. Stimulation of H9c2, cardiac myoblast cells, with
fetal calf serum, which can induce myocyte
hypertrophy, upregulated Epac1
protein expression. We also demonstrated that
Epac was the limiting moiety, relative to Rap, in the
Epac-Rap signaling pathway in terms of stoichiometry and that
Epac stimulation led to the activation of ERK1/2. Our data suggest the functional involvement of
Epac in organogenesis and also in physiological as well as pathophysiological processes, such as
cardiac hypertrophy. Furthermore, our results suggest the importance of the stoichiometry of
Epac over that of Rap in cellular
biological effects.