A member of the phosphodiesterase (PDE)7 family with high affinity and spec
ificity for cAMP has been identified. Based on sequence homologies, we desi
gnate this PDE as PDE7B. The full-length cDNA of PDE7B is 2399 bp, and its
ORF sequence predicts a protein of 446 amino acids with a molecular mass of
50.1 kDa. Comparison of the predicted protein sequences of PDE7A and PDE7B
reveals an identity of 70% in the catalytic domain. Northern blotting indi
cates that the mRNA of PDE7B is 5.6 kb. It is most highly expressed in panc
reas followed by brain, heart, thyroid, skeletal muscle, eye, ovary, submax
illary gland, epididymus, and liver. Recombinant PDE7B protein expressed in
a Baculovirus expression system is specific for cAMP with a K-m of 0.03 mu
M. Within a series of common PDE inhibitors, it is most potently inhibited
by 3-isobutyl-1-methylxanthine with an IC50 of 2.1 mu M. It is also inhibi
ted by papaverine, dipyridamole, and SCH51866 at higher doses. PDE7A and PD
E7B exhibit the same general pattern of inhibitor specificity among the sev
eral drugs tested. However, differences in IC50 for some of the drugs sugge
st that isozyme selective inhibitors can be developed.