Mechanistic insights into the role of alpha1adrenergic receptors in lower urinary tract symptoms.
Although alpha(1)AR 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 alpha(1)ARs play a critical role in bladder dysfunction and recent data suggest that alpha(1)AR subtype switching may play a key role in this pathophysiology, providing support for use of alpha(1)(d)AR-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 alpha(1)AR antagonists and other pharmacodynamic factors.
Michelotti
Gregory A
GA
Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710, USA. miche007@mc.duke.edu
Schwinn
Debra A
DA
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008875:Middle Aged; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D015398:Signal Transduction; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy / Q000503:physiopathology; D014570:Urologic Diseases / Q000188:drug therapy / Q000503:physiopathology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1