Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum

Küthe, Andrea; Eckel, H.; Stief, Christian G.; Ückert, Stefan; Forssmann, W. G.; Jonas, Udo; Mägert, Hans J.

doi:10.1016/s0009-2797(99)00074-5

Cited by 11 publications

(4 citation statements)

References 16 publications

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“…Because of their central role in smooth muscle tone regulation and the considerable variation of PDE isoenzymes with respect to species and tissues, PDEs have become an attractive target for drug development. In human cavernosal tissue, at least 13 isoenzymes have been identified, including PDE3 (cGMP-inhibited cAMP PDE), PDE4 (cAMP-specific PDE), and PDE5 (cGMP-specific PDE) (Kü the et al, 1999(Kü the et al, , 2000(Kü the et al, , 2001. Functionally, PDE 3A and 5A seem to be the most important (Kü the et al, 830 Francis et al, 2010).…”

Section: J Nitric Oxide and Cgmp Signalingmentioning

confidence: 99%

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Andersson

2011

Pharmacological Reviews

315

326

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Section: J Nitric Oxide and Cgmp Signalingmentioning

confidence: 99%

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Andersson

2011

Pharmacological Reviews

315

326

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“…Gs‐α and Gi‐α are two distinct G‐proteins which mediate the stimulation and inhibition of AC and thus are involved in the regulation of cavernous smooth muscle tone [28]. cAMP is further regulated by its degradation by cAMP‐binding PDEs (PDE3A and PDE4), and PDE3A is highly expressed in CC [29–32]. Thus, the relaxation effect of VIP on cavernous smooth muscle depends on VPAC2, G‐proteins, and PDE3A.…”

Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats

Zhang

et al. 2010

BJU International

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PDE3A in rat corpus cavernosum (CC) was qualified by real-time PCR and Western blot analysis. RESULTS• Castration reduced erectile function while testosterone restored it. VIP improved erectile function in a dose-dependent manner.• High-dose VIP significantly enhanced erectile function in castrated rats and there was no difference of ICP/MAP among three groups after injection of high-dose VIP.• Low-dose VIP also resulted in a higher improvement of erectile function in castrated rats, although the ICP/MAP was lower in these rats than in the other two groups. VPAC2 and Gs-α were up-regulated while Gi-α and PDE3A were down-regulated in CC of castrated rats. CONCLUSION• VIP improves erectile function much more significantly in hypogonadal condition, mainly due to the higher expression of VPAC2, Gs-α , and lower expression of Gi-α and PDE3A in CC of castrated rats. Androgen may negatively regulate the erectile effect of VIP. KEYWORDS androgen, vasoactive intestinal polypeptide, erectile function, castration, signaling pathwayWhat's known on the subject? and What does the study add? Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter, and our previous study found that the mRNA expression of VIP was independent of androgens.The present study further investigated the vivo effect of VIP on erection. We found that not only the expression of VIP was independent of androgens, but also the effect of VIP on erection was independent of androgens. In fact, we found that VIP played a more significant role on erection in castrated rats than in normal rats. OBJECTIVE

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“…6 Phosphodiesterase 3 (PDE3) degrades cAMP and is localized to some extent in the corpus cavernosum. 12,13 Agents which inhibit PDE3 and increase cAMP could also have the potential to induce erections. One such agent is milrinone, which is currently being evaluated for erectile dysfunction.…”

Section: Introductionmentioning

confidence: 99%

A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection

Bischoff

Schneider

2001

Int J Impot Res

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Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show potential for the treatment of erectile dysfunction. Erection was assessed by measuring the length of uncovered penile mucosa before and after the intravenous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors vardena®l 6 HCl (hereafter called vardena®l) and sildena®l were given intravenously, and measurements were taken for 0 ± 5 h. The effects of phentolamine and milrinone were also evaluated. Vardena®l (0.1 ± 3 mgakg) induced dose-dependent penile erections in conscious rabbits following i.v. administration. The ef®cacy of vardena®l was potentiated, and the minimal effective dose was reduced signi®cantly to 0.01 mgakg by simultaneous administration of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect. Sildena®l was effective in this model after i.v. administration. The a-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mgakg i.v.) induced erections with a slower t max compared with vardena®l and sildena®l. Intravenous administration of the PDE3 inhibitor milrinone (1 mgakg i.v.) was less effective than the PDE5 inhibitor vardena®l. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treatment of erectile dysfunction. This was demonstrated using compounds that target different signaling pathways that induce smooth muscle relaxation in the penis.

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Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum

Cited by 11 publications

References 16 publications

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats

A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection

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