The human genome contains at least 21 genes involved in determining the intracellular levels of cAMP and cGMP by the expression of phosphodiesterase proteins or PDEs. These PDEs are grouped into at least 11 functional subfamilies, named PDE1-PDE11. PDEs are enzymes that hydrolyze cyclic adenosine 3,5-monophosphate (cAMP) and cyclic guanosine 3,5-monophospahate (cGMP), which are intracellular second messengers, into AMP and GMP. These second messengers control many physiological processes.
The cAMP is formed from ATP by the enzyme adenylyl cyclase and cGMP is formed from GTP by the enzyme guanylyl cyclase which are either membrane bound or soluble in the cytosol. When soluble it functions as a receptor for nitric oxide (NO) (see figure 1).
Formation of cGMP initiates several reactions in the body including influence on cGMP ion channels, cGMP binding proteins and protein kinase G (PKG). The effect on PKG reduces levels of calcium leading to relaxation of smooth muscles (see figure 2). 
The PDE5 enzyme is specific for cGMP which means it only hydrolyzes cGMP but not cAMP. The selectivity is mediated through an intricate network of hydrogen bonding which is favorable for cGMP but unfavorable for cAMP in PDE5.
By inhibition of PDE5 enzyme the cGMP concentration will be raised and can therefore increase the relaxation of smooth muscles. PDE5 has only one subtype, PDE5A, of which there are 4 isoforms in humans called PDE5A1-4. The difference in PDE5A1-3 isoforms is only in the 5´ end of the mRNA and corresponding N-terminal of the protein.