Role of adenosine and P2 receptors in the penile tumescence in anesthetized dogs

Noto, Tsunehisa; Inoue, Hirokazu; Mochida, Hideki; Kikkawa, Kohei

doi:10.1016/s0014-2999(01)01167-0

Cited by 32 publications

(49 citation statements)

References 17 publications

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“…Adenosine may also relax HCC strips acting directly through A 2A receptors on smooth muscle fibers in an NO-independent manner, like that observed in the rabbit penile vessels (Mantelli et al, 1995) and in the anesthetized dog (Noto et al, 2001).…”

Section: Discussionmentioning

confidence: 63%

“…As far as we know, this is the first study to suggest the involvement of two subtypes of adenosine receptors, high-affinity A 2A and low-affinity A 2B , in the relaxation of cavernosal vessels of the human penis. Receptor heterogeneity might explain some controversies found in the literature concerning the efficacy profile of nonselective adenosine agonists (e.g., NECA) on erectile tissues of human and other species (Mantelli et al, 1995;Filippi et al, 2000;Andersson, 2001;Noto et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

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Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction

Faria

Magalhães-Cardoso²,

Lafuente-de-Carvalho³

et al. 2006

J Pharmacol Exp Ther

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Although adenosine has been implicated in penile erection in human males, the receptor subtype responsible for adenosine regulation of human corpus cavernosum (HCC) smooth muscle tone is still a matter of debate. Using selective adenosine agonists and antagonists, we aimed at characterizing the adenosine receptors mediating relaxation of precontracted (with 1 M phenylephrine) HCC strips. HCC specimens were collected from control subjects (organ donors) and from patients with severe vasculogenic erectile dysfunction (ED). In control subjects, adenosine and 5Ј-N-ethyl-carboxamide adenosine (NECA) fully relaxed HCC. The selective A 2A receptor agonist 2-[4-(2-p-carboxy ethyl)phenylamino]-5Ј-N-ethylcarboxamido adenosine (CGS21680C) produced only a partial relaxation (30 -50%) of HCC, which could be further enhanced by simultaneous application of 100 M NECA. The selective A 2B receptor antagonist N-(4-acetylphenyl)-2- [4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-il) (ZM241385) (50 nM) consistently reduced the actions of both agonists. In contrast to CGS21680C, NECAinduced relaxation was attenuated when endothelial production of NO and prostanoids was reduced by 100 M N G -nitro-Larginine and 10 M indomethacin, respectively. HCC strips from patients with vasculogenic ED were partially resistant to NECA but kept relaxation to CGS21680C; the remaining effect was sensitive to blockade of A 2A receptors with 50 nM ZM241385. Data suggest that adenosine regulates HCC smooth muscle tone through the activation of two receptor populations, CGS21680C-sensitive (A 2A ) and -insensitive (A 2B ) receptors, located on smooth muscle fibers and on endothelial cells, respectively. Endothelial dysfunction may be correlated with a loss of adenosine A 2B receptor activity in penile vessels from men with vasculogenic ED.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction

Faria

Magalhães-Cardoso²,

Lafuente-de-Carvalho³

et al. 2006

J Pharmacol Exp Ther

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“…However, studies of the role of adenosine signaling in penile vascular function are very limited. Earlier studies in several animal species, including humans (20), showed that intracavernous injection of adenosine resulted in tumescence and penile erection (14)(15)(16)(17)(18)(19). These findings suggest that adenosine may contribute to penile erection.…”

Section: Discussionmentioning

confidence: 91%

“…Second, both have a very short half life (<10 s) (13). Third, both induce cyclic nucleotide second messengers and penile erection (14)(15)(16)(17)(18)(19). Specifically, adenosine functions through G protein-coupled receptors to modulate adenylyl cyclase and the synthesis of cAMP.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, adenosine-mediated cAMP induction and NO-mediated cGMP induction are capable of inducing protein kinase A and protein kinase G, respectively, resulting in decreased calcium/calmodulin-dependent myosin light chain phosphorylation and enhanced smooth muscle relaxation (14). Earlier studies in multiple animal species, including humans (20), showed that intracavernous injection of adenosine resulted in tumescence and penile erection (14)(15)(16)(17)(18)(19). Theophylline, an adenosine receptor antagonist, inhibited adenosine-induced penile tumescence (21).…”

Section: Introductionmentioning

confidence: 99%

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Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

Mi¹,

Abbasi²,

Zhang³

et al. 2008

J. Clin. Invest.

136

221

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Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A 2B adenosine receptor-mediated (A 2B R-mediated) cAMP and cGMP induction was required for elevated adenosine-induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A 2B R activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A 2B R signaling in both Ada -/-and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A 2B R activation may prove beneficial in the treatment of this disorder.

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Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction

Xiong,

Qin,

Wei

et al. 2024

Advanced Science

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The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single‐cell RNA sequencing of human corpus cavernosum, adenosine deaminase (ADA) and adenosine receptors knock‐out mice (ADA−/−, A1−/−, A2a−/−, A2b−/−, and A3−/−), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine‐induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age‐related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus‐induced ED. In single‐cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock‐out abolishes adenosine‐induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF‐1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60–6583 improves erectile function and down‐regulates HIF‐1α and TGF‐β. Administering Dipyridamole (40 mg Kg−1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine‐induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.

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Role of adenosine and P2 receptors in the penile tumescence in anesthetized dogs

Cited by 32 publications

References 17 publications

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction

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Role of adenosine and P2 receptors in the penile tumescence in anesthetized dogs

Cited by 32 publications

References 17 publications

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A2BReceptor Dysfunction

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A2BReceptor Dysfunction

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction

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Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction