The paper describes the discovery and characterization of a polymorphism in the promoter region of the phosphodiesterase 3A, or PDE3A
, gene, which encodes the target of Type 3 phosphodiesterase inhibitors, or PDE3Is.
On the other hand, PDE3A, the target of anagrelide, is highly expressed in epithelial cancer cell lines, including lung, colon, and cervical cancer  and its targeted inhibition is evaluated for redirection of PDE3 inhibitors in anticancer treatment  as well as an intense search for new ones .
Rees et al., "Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics," Nature Chemical Biology, vol.
Mendelian forms of hypertension and germline mutations causing early-onset hypertension have highlighted biological pathways that involve renal salt handling (WNK1, WNK4, KLHL3, and CUL3), ion transport (CACNA1D, CACNA1H, KCNJ5, SCNN1B, and SCNN1G), corticosteroidogenesis (CYP11B2, HSD11B2, NR3C2, CYP11B1, and CYP17A1), and vascular tone (PDE3A) to regulate blood [41-44].
Luft et al., "PDE3A mutations cause autosomal dominant hypertension with brachydactyly," Nature Genetics, vol.
Heterozygous mutations in PDE3A have been identified in patients affected with HTNB (51).
IUGR has also been described in other iPPSD, such as acrodysostosis with mutations in PRKAR1A or PDE4D, and in patients with mutations in PDE3A (40,41,49,51).
Cumulus cells are the main source of cGMP and its transmission via gap junctions results in inhibiting phosphodiesterase 3A (PDE3A
) which in turn leads to an increase in cAMP level and meiotic arrest (34).
For example, miR-128 has 6 predicted gene targets [pyruvate dehydrogenase kinase, isozyme 1 (PDK1); pyruvate dehydrogenase kinase isozyme 2 (PDK2); MTOR; phosphodiesterase 3A, cGMP-inhibited (PDE3A
); phosphodiesterase 3B, cGMP-inhibited (PDE3B); FOXO1], and miR-141 is predicted to target 5 genes [PTEN; PDK2; cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A); CDKN1B;PDE3B].
For instance, muscarinic acetylcholine receptor M2 (CHRM2), neuronal acetylcholine receptor subunit [alpha]-2 (CHRNA2), gamma-aminobutyric acid receptor subunit alpha-3 (GABRA3), NO synthase, inducible (NOS2), cGMP-inhibited 3'?,5'-cyclic phosphodiesterase A (PDE3A
), and sodium-dependent dopamine transporter (SLC6A3) recorded beyond average mRNA expression in all six groups.
In consistence with these findings, knockdown of the cAMP-hydrolyzing PDE3A
was sufficient to induce apoptosis in cultured primary cardiac myocytes , possibly through PKA-dependent stabilization of inducible cAMP early repressor (ICER) .
Additionally, two other diseases are caused by the defects involved in signaling pathway of Gs[alpha], acrodysostosis caused by heterozygous mutations in PRKAR1A and PDE4D (7,8) and hypertension and brachydactyly syndrome (HTNB) caused by heterozygous mutations in PDE3A
have been identified (9).