Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction

Authors

Yang Xiong
Feng Qin
Shanzun Wei
Xingliang Yang
Jun Li
Changjing Wu
Fuxun Zhang
Jiuhong Yuan

Language

English

Publication Date

8-1-2024

Journal

Advanced Science

DOI

10.1002/advs.202306514

PMID

38874549

PMCID

PMC11321695

PubMedCentral® Posted Date

6-14-2024

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Animals, Humans, Male, Mice, Rats, Adenosine, Disease Models, Animal, Erectile Dysfunction, Mice, Knockout, Penile Erection, Penis, Rats, Sprague-Dawley, Receptor, Adenosine A2B, adenosine, A2b receptor, dipyridamole, penile rehabilitation, refractory erectile dysfunction

Published Open-Access

yes

Recommended Citation

Xiong, Yang; Qin, Feng; Wei, Shanzun; et al., "Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction" (2024). Faculty, Staff and Student Publications. 6130.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6130