Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3′,5′-cyclic nucleotide phosphodiesterase

Loughney, Kate; Hill, Teresa; Florio, Vincent A.; Uher, L.; Rosman, Guy J; Wolda, Sharon L.; Jones, Bryan A.; Howard, Monique L.; McAllister-Lucas, Linda M.; Sonnenburg, William K.; Francis, Sharron H.; Corbin, Jackie D.; Beavo, Joseph A.; Ferguson, K.

doi:10.1016/s0378-1119(98)00303-5

Cited by 206 publications

(154 citation statements)

References 29 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…Since PDE-5 is found in the brain as well as in the corpus cavernosum, tadalafil and other PDE-5 inhibitors might exert side effects in the CNS by crossing the blood-brain barrier. 11,12 There are several hypotheses concerning the aetiology of TGA. Lewis proposed that an increased central venous return during Valsalva-like manoeuvres may cause hippocampal oligaemia due to venous congestion.…”

Section: Discussionmentioning

confidence: 99%

Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association?

Schiefer¹,

Sparing²

2005

Int J Impot Res

View full text Add to dashboard Cite

Inhibitors of phosphodiesterase type 5 (PDE-5) are well established as an oral treatment for the majority of patients with erectile dysfunction (ED). PDE-5 is found in high concentration in smooth muscle cells of the corpora cavernosa. However, enzymes of the PDE family are also expressed in various other tissues, including the brain. Little is known about its effects on the central nervous system (CNS), although it has been suggested that PDE-5 inhibitors might cross the blood-brain barrier. Side effects, such as headache, nasal congestion, flushing, nausea, are much more common. We describe a patient who had a transient global amnesia (TGA) after his first-ever use of tadalafil, a potent PDE-5 inhibitor. Despite the fact that the aetiology of TGA has not entirely been clarified at present, we consider the hypothesis of a causal relationship as tempting with respect to the current hypotheses of TGA pathophysiology. This case, together with others, suggests that PDE-5 inhibitors might be capable of exerting adverse effects in the CNS. Physicians should be aware of the possibility of neurological disturbances when prescribing PDE-5 inhibitors for ED.

show abstract

Section: Discussionmentioning

confidence: 99%

Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association?

Schiefer¹,

Sparing²

2005

Int J Impot Res

View full text Add to dashboard Cite

show abstract

“…18 PDE 5 has been found in the smooth muscles of the penile corpora cavernosa, however it may not be present in human spermatozoa. 5 The doses of sildena®l used to incubate the spermatozoa samples were chosen according to the pharmacokinetic characteristics of this PDE inhibitor. An orally administered dose of sildena®l is rapidly absorbed, with maximum plasma levels occurring approximately 1 h after administration.…”

Section: Discussionmentioning

confidence: 99%

“…4 Type-5 PDE isozyme is predominantly expressed in the penile corpus cavernosum, however it has been localized in various other tissues, such as brain, lung, kidney and placenta. 5 Although little is known about the physiological role of PDE and its isoforms in human spermatozoa, its inhibition has been reported to stimulate sperm motility, suggesting an association between the levels of cytosolic nucleotides and sperm motion. 2,6 Human spermatozoa has been shown to have two distinct PDE isoforms (PDE 1 and PDE 4).…”

Section: Introductionmentioning

confidence: 99%

The effect of sildenafil on human sperm motion and function from normal and infertile men

et al. 2000

View full text Add to dashboard Cite

The aim of this report was to study the effect of sildena®l, a speci®c type-5 phosphodiesterase inhibitor, on human sperm motility, viability, membrane integrity and sperm penetration assay.Spermatozoa were obtained from normal donors (n 6) and infertile men (n 6) were washed using a single Percoll (80%) gradient, suspended in Ham's F-10 medium, and incubated with various doses of sildena®l (125, 250 and 750 ngaml); pentoxifylline (3 mM) was used as a positive control, and Ham's F-10 was used as a reagent control. Sperm motility, grade, viability, membrane integrity (by hypo-osmotic swelling test), and motion evaluation were carried out at various time intervals. Hamster ova sperm penetration assay (SPA) was used to evaluate overall sperm function.Sildena®l did not affect sperm motility, viability or membrane integrity under these conditions as compared to our Ham's control (P b 0.05). Incubation with pentoxifylline signi®cantly enhanced sperm motility (P`0.05) and viability without affecting membrane integrity (P`0.05). Sperm incubated with sildena®l and pentoxifylline from both normal donors and infertile patients demonstrated no signi®cant change in sperm penetration assay from respective controls.In conclusion, sildena®l, at the doses evaluated, did not signi®cantly alter the motility, viability, membrane integrity or sperm penetration characteristics of human spermatozoa from normal donors and infertile patients.

show abstract

“…7 Two PDE5 isoforms, PDE5A1 and PDE5A2, have been identified in humans and dogs. 1,4 More recently, a third isoform, PDE5A3, was identified in humans. 8 The three human PDE5 isoforms differ only in the 5 0 end of the mRNA and the corresponding N-terminal of the protein.…”

Section: Introductionmentioning

confidence: 99%

“…The human PDE5 gene is located on chromosome 4q26 4,5 and initially reported to contain 21 exons spanning approximately 100 kilobases. 5 The current identification of PDE5 isoforms should increase that number to 23 exons, with the first three exons being alternative first exons encoding the isoformspecific sequences.…”

Section: Introductionmentioning

confidence: 99%

Tissue expression, distribution, and regulation of PDE5

Lin

2004

Int J Impot Res

View full text Add to dashboard Cite

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.

show abstract

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3′,5′-cyclic nucleotide phosphodiesterase

Cited by 206 publications

References 29 publications

Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association?

Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association?

The effect of sildenafil on human sperm motion and function from normal and infertile men

Tissue expression, distribution, and regulation of PDE5

Contact Info

Product

Resources

About