Tissue expression, distribution, and regulation of PDE5.
Phosphodiesterase 5 (PDE5) has been identified in many species. The three isoforms, PDE5A1, PDE5A2, and PDE5A3, differ only in their N-terminal sequence. PDE5A1 and PDE5A2 are ubiquitous, but PDE5A3 is specific to smooth muscle. The initial three exons (A1-A3-A2) of PDE5A, located on chromosome 4q26, are alternative first exons encoding the isoform-specific sequences. The PDE5A promoter overlaps with the A1-specific exon, while the PDE5A2 promoter is located between the A3- and A2-specific exons. Both respond to cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP) stimulation. The PDE5A2 promoter contains an Sp1-binding sequence critical for basal and cGMP/cAMP-inducible promoter activities. PDE5A is induced by adjacent sequences (enhancers) containing Sp1-binding sites. The potential role of PDE5A promoters in the tachyphylaxis effect of PDE5 inhibitors is currently being investigated. Preliminary data suggest that hypoxia might down-regulate PDE5A promoters, implying an involvement of PDE5 in stuttering priapism.
Lin
C-S
CS
Department of Urology, University of California, San Francisco, CA 94115, USA. clin@urol.ucsf.edu
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000032:analysis* / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D002894:Chromosomes, Human, Pair 4; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics; D008297:Male; D009130:Muscle, Smooth / Q000201:enzymology; D009928:Organ Specificity; D011317:Priapism / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000235:genetics; D014018:Tissue Distribution; D014157:Transcription Factors
D007527:Isoenzymes; D014157:Transcription Factors; D000242:Cyclic AMP; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006152:Cyclic GMP