Tissue expression, distribution, and regulation of PDE5
Author:
- 1 June 2004
- journal article
- review article
- Published by Springer Nature in International Journal Of Impotence Research
- Vol. 16 (S1) , S8-S10
Abstract
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.Keywords
This publication has 14 references indexed in Scilit:
- Cardiac phosphodiesterase 5 (cGMP‐specific) modulates β‐adrenergic signaling in vivo and is down‐regulated in heart failureThe FASEB Journal, 2001
- Regulation of Human PDE5A2 Intronic Promoter by cAMP and cGMP: Identification of a Critical Sp1-Binding SiteBiochemical and Biophysical Research Communications, 2001
- Identification and Regulation of Human PDE5A Gene PromoterBiochemical and Biophysical Research Communications, 2001
- Identification of Three Alternative First Exons and an Intronic Promoter of Human PDE5A GeneBiochemical and Biophysical Research Communications, 2000
- Expression of Three Isoforms of cGMP-Binding cGMP-Specific Phosphodiesterase (PDE5) in Human Penile CavernosumBiochemical and Biophysical Research Communications, 2000
- Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitroThe American Journal of Cardiology, 1999
- Novel Alternative Splice Variants of cGMP-binding cGMP-specific PhosphodiesteraseJournal of Biological Chemistry, 1998
- Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3′,5′-cyclic nucleotide phosphodiesteraseGene, 1998
- Expression, structure and chromosomal localization of the human cGMP‐binding cGMP‐specific phosphodiesterase PDE5A geneEuropean Journal of Biochemistry, 1998
- Expression of Rat cGMP‐Binding cGMP‐Specific Phosphodiesterase mRNA in Purkinje Cell Layers During Postnatal Neuronal DevelopmentEuropean Journal of Biochemistry, 1997