Therapeutic modulation of urinary bladder function: multiple targets at multiple levels

Annu Rev Pharmacol Toxicol. 2015;55:269-87. doi: 10.1146/annurev-pharmtox-010814-124536. Epub 2014 Sep 10.

Abstract

Storage dysfunction of the urinary bladder, specifically overactive bladder syndrome, is a condition that occurs frequently in the general population. Historically, pathophysiological and treatment concepts related to overactive bladder have focused on smooth muscle cells. Although these are the central effector, numerous anatomic structures are involved in their regulation, including the urothelium, afferent and efferent nerves, and the central nervous system. Each of these structures involves receptors for—and the urothelium itself also releases—many mediators. Moreover, hypoperfusion, hypertrophy, and fibrosis can affect bladder function. Established treatments such as muscarinic antagonists, β-adrenoceptor agonists, and onabotulinumtoxinA each work in part through their effects on the urothelium and afferent nerves, as do α1-adrenoceptor antagonists in the treatment of voiding dysfunction associated with benign prostatic hyperplasia; however, none of these treatments are specifically targeted to the urothelium and afferent nerves. It remains to be explored whether future treatments that specifically act at one of these structures will provide a therapeutic advantage.

Keywords: afferent nerve; muscarinic receptor antagonist; urothelium; α1-adrenoceptor antagonist; β-adrenoceptor agonist.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use
  • Adrenergic beta-Agonists / therapeutic use
  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Central Nervous System / physiopathology
  • Humans
  • Muscarinic Antagonists / therapeutic use
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / innervation
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiopathology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism
  • Neurons, Efferent / drug effects
  • Neurons, Efferent / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Urinary Bladder / drug effects*
  • Urinary Bladder / innervation
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder / physiopathology
  • Urinary Bladder Diseases / diagnosis
  • Urinary Bladder Diseases / drug therapy*
  • Urinary Bladder Diseases / metabolism
  • Urinary Bladder Diseases / physiopathology
  • Urodynamics / drug effects
  • Urological Agents / adverse effects
  • Urological Agents / therapeutic use*
  • Urothelium / drug effects*
  • Urothelium / innervation
  • Urothelium / metabolism
  • Urothelium / physiopathology

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Muscarinic Antagonists
  • Urological Agents