Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Int J Impot Res. 2002 Feb;14(1):15-24.

Human PDE5A gene encodes three PDE5 isoforms from two alternate promoters.

Author information

  • 1Knuppe Molecular Urology Laboratory, School of Medicine, University of California, San Francisco, CA 94143-1695, USA. clin@urol.ucsf.edu

Abstract

Sildenafil improves erectile function by inhibiting the cGMP-catalytic activity of phosphodiesterase type V (PDE5). We used rapid amplification of cDNA Ends-polymerase chain reaction (RACE-PCR) to isolate three PDE5 isoforms from human corpus cavernosum. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis on eight human cavernous tissue samples showed that all samples expressed the PDE5A1 at a lower level than the PDE5A2 isoform. Five samples expressed the PDE5A3 isoform at various levels while the other three did not. Analysis on non-penile tissues showed that all tissues expressed the A1 and A2 isoforms while only those that have substantial amounts of smooth muscle expressed the A3 isoform. Cloning and sequencing of the PDE5A gene showed that the isoform-specific 5'-ends of the PDE5 mRNAs are encoded from three alternative first exons arranged in the order of A1-A3-A2. Promoter activities were detected upstream from the A1-specific exon and in the intron preceding the A2-specific exon. The upstream PDE5A promoter is expected to direct the expression of all three PDE5 isoforms while the intronic PDE5A2 promoter only the A2 isoform. Both promoters were upregulated by increasing concentrations of either cAMP or cGMP. Several transcription factor AP2 and Sp1-binding sequences identified in the promoters are likely to be the mediators of cAMP/cGMP-responsiveness.

PMID:
11896473
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk