“…PDE family–selective inhibitors are available and have contributed significantly to our understanding of the role of different PDEs in the compartmentalization of cAMP ( Houslay et al, 2005 ; Lugnier, 2006 ; Francis et al, 2011b ; Page and Spina, 2012 ; Kokkonen and Kass, 2017 ). For example, in rat cardiac myocytes, PDE3 and PDE4 enzymes show a very distinct localization, and inhibition of PDE4, but not inhibition of PDE3, results in significant increase in cAMP levels generated by β -agonists ( Mongillo et al, 2004 ; Bedioune et al, 2017 ; Conti, 2017 ). Currently available pharmacological inhibitors do not discriminate between different isoforms within the same PDE family.…”