PGE2 receptors in detrusor muscle: Drugging the undruggable for urgency.

Ruida Hou, Ying Yu, Jianxiong Jiang

Biochemical pharmacology 2021 Feb

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Overactive bladder (OAB) syndrome is a prevalent condition of the lower urinary tract that causes symptoms, such as urinary frequency, urinary urgency, urge incontinence, and nocturia, and disproportionately affects women and the elderly. Current medications for OAB merely provide symptomatic relief with considerable limitations, as they are no more than moderately effective, not to mention that they may cause substantial adverse effects. Identifying novel molecular targets to facilitate the development of new medical therapies with higher efficacy and safety for OAB is in an urgent unmet need. Although the molecular mechanisms underlying the pathophysiology of OAB largely remain elusive and are likely multifactorial, mounting evidence from preclinical studies over the past decade reveals that the pro-inflammatory pathways engaging cyclooxygenases and their prostanoid products, particularly the prostaglandin E2 (PGE2), may play essential roles in the progression of OAB. The goals of this review are to summarize recent progresses in our knowledge on the pathogenic roles of PGE2 in the OAB and to provide new mechanistic insights into the signaling pathways transduced by its four G-protein-coupled receptors (GPCRs), i.e., EP1-EP4, in the overactive detrusor smooth muscle. We also discuss the feasibility of targeting these GPCRs as an emerging strategy to treat OAB with better therapeutic specificity than the current medications. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Ruida Hou, Ying Yu, Jianxiong Jiang. PGE2 receptors in detrusor muscle: Drugging the undruggable for urgency. Biochemical pharmacology. 2021 Feb;184:114363