Reagents and animals

All chemicals and materials were from MilliporeSigma (Burlington, MA, USA), VWR (Radnor, PA, USA), and Tocris (Ellisville, MO, USA) unless noted otherwise and were at least of reagent grade. Animal use and welfare adhered to the Guide for the Care and Use of Laboratory Animals [National Institutes of Health (NIH), Bethesda, MD, USA] following protocols reviewed and approved by the Animal Care and Use Committee of the University of Texas Health Science Center at Houston. For experiments, 6- to 10-wk-old Epac wild-type (WT), and Epac1^−/−, and Epac2^−/− mice were used. Generation of mice lacking Epac isoforms has been previously described (18, 19).