ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
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- Alternative adenosine Receptor activation: The netrin-Adora2b link.Frontiers in pharmacology · 2022Review
- Adenosine: a partially discovered medicinal agent.Future journal of pharmaceutical sciences · 2021Review
- Collective invasion induced by an autocrine purinergic loop through connexin-43 hemichannels.The Journal of cell biology · 2020Article
- Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies.Acta pharmacologica Sinica · 2020Article
- PI3K/Akt pathway-mediated HO-1 induction regulates mitochondrial quality control and attenuates endotoxin-induced acute lung injury.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Metabolic syndrome in rats is associated with erectile dysfunction by impairing PI3K/Akt/eNOS activity.Scientific reports · 2017Article
- The arterial microenvironment: the where and why of atherosclerosis.The Biochemical journal · 2016Review
- Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery.The Journal of pharmacology and experimental therapeutics · 2016Article
- Beneficial and detrimental role of adenosine signaling in diseases and therapy.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Review
- Nitrergic Mechanisms for Management of Recurrent Priapism.Sexual medicine reviews · 2015Article
- Adenosine signaling promotes hematopoietic stem and progenitor cell emergence.The Journal of experimental medicine · 2015Article
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- Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway.Oxidative medicine and cellular longevity · 2015Article
- Probing biased/partial agonism at the G protein-coupled A(2B) adenosine receptor.Biochemical pharmacology · 2014Article
- Role of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the renal 2',3'-cAMP-adenosine pathway.American journal of physiology. Renal physiology · 2014Article
- Excess adenosine A2B receptor signaling contributes to priapism through HIF-1α mediated reduction of PDE5 gene expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Normal penile erection is under the control of multiple factors and signaling pathways. Although adenosine signaling is implicated in normal and abnormal penile erection, the exact role and the underlying mechanism for adenosine signaling in penile physiology remain elusive. Here we report that shear stress leads to increased adenosine release from endothelial cells. Subsequently, we determined that ecto-5'-nucleotidase (CD73) is a key enzyme required for the production of elevated adenosine from ATP released by shear-stressed endothelial cells. Mechanistically, we demonstrate that shear stress-mediated elevated adenosine functions through the adenosine A(2B) receptor (A(2B)R) to activate the PI3K/AKT signaling cascade and subsequent increased endothelial nitric oxide synthase (eNOS) phosphorylation. These in vitro studies led us to discover further that adenosine was induced during sustained penile erection and contributes to PI3K/AKT activation and subsequent eNOS phosphorylation via A(2B)R signaling in intact animal. Finally, we demonstrate that lowering adenosine in wild-type mice or genetic deletion of A(2B)R in mutant mice significantly attenuated PI3K/AKT activation, eNOS phosphorylation, and subsequent impaired penile erection featured with the reduction of ratio of maximal intracavernosal pressure to systemic arterial pressure from 0.49 ± 0.03 to 0.41 ± 0.05 and 0.38 ± 0.04, respectively (both P<0.05). Overall, using biochemical, cellular, genetic, and physiological approaches, our findings reveal that adenosine is a novel molecule signaling via A(2B)R activation, contributing to penile erection via PI3K/AKT-dependent eNOS activation. These studies suggest that this signaling pathway may be a novel therapeutic target for erectile disorders.
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Registered trials
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