Identification of human PDE7B, a cAMP-specific phosphodiesterase.
We isolated a human cAMP-specific phosphodiesterase (PDE7B) cDNA from human caudate nucleus. The human PDE7B was composed of 450 amino acid residues with a molecular mass of 51,835 Da. The deduced amino acid sequence of human PDE7B was 64.1% identical to that of human PDE7A (67.1% identity in the catalytic region). Northern blot analysis demonstrated that PDE7B transcripts were abundantly expressed in the putamen, caudate nucleus, and heart followed by skeletal muscle, pancreas, and occipital pole. Recombinant PDE7B expressed in transfected COS-7 cells had a low cAMP K(m) value of 0. 13 microM, which is similar to the K(m) value of recombinant human PDE7A expressed in transfected COS-7 cells. Interestingly, the relative V(max) value of recombinant PDE7B was half to one-third of recombinant PDE7A. The PDE7B activity was inhibited by dipyridamole and SCH51866, with IC(50) values of 1.1 microM and 1.5 microM, respectively. Thus, the PDE7B exhibited unique tissue distribution in humans and kinetic profiles. Human PDE7B showed the lowest K(m) values compared to the other cAMP-hydrolyzing PDEs which have been reported to be expressed in the brain. Therefore, human PDE7B may be involved in the control of cAMP-mediated neural activity and cAMP metabolism in the brain.
Sasaki
T
T
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-50, Kawagishi-2-chome, Toda, Saitama, 335-8505, Japan.
Kotera
J
J
Yuasa
K
K
Omori
K
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D019556:COS Cells; D003001:Cloning, Molecular; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D004176:Dipyridamole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010455:Peptides; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D004791:Enzyme Inhibitors; D007093:Imidazoles; D009842:Oligopeptides; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004176:Dipyridamole; C085706:FLAG peptide; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517458:PDE7A protein, human; C517463:PDE7B protein, human; C096501:SCH 51866