Mechanistic insights into the role of α1-adrenergic receptors in lower urinary tract symptoms

Although α1AR antagonists have been used for more than two decades to treat lower urinary tract symptoms (LUTS), we have little understanding of the mechanistic basis of their efficacy and their role in the development of LUTS. It is clear that α1ARs play a critical role in bladder dysfunction and recent data suggest that α1AR subtype switching may play a key role in this pathophysiology, providing support for use of α1dAR-selective antagonists in treating irritative symptoms. This review seeks to summarize current levels of understanding in this field and discusses new concepts that suggest increased levels of complexity involving cross-talk in multiple receptor systems. Effective therapeutic modalities likely will involve increased subtype selective α1AR antagonists and other pharmacodynamic factors.