New insights into the pharmacology of the bladder.
OBJECTIVE
Pharmacotherapy of a number of bladder disorders has traditionally focused on targeting the 'sensory' component or bladder nerves and the smooth muscle. This review aims to provide an insight into recent (experimental and clinical) developments in mechanisms of existing therapies as well as novel targets.


RESULTS
Traditionally, sensory signaling in the urinary bladder has been attributed to activation of bladder afferents, but new findings have pointed to the urothelium and interstitial cells as key participants in the transduction of sensory events. Recent advances provide strong support for the development of subtype selective receptor agonists/antagonists, the modulation of signal transduction cascades and new and expanded uses for various neurotoxins.


CONCLUSIONS
The development of therapeutic options for the treatment of a number of bladder disorders is complicated, and most treatments are associated with an increased incidence of side effects or lack of specificity. Recent studies suggest that selective targeting of receptors/ion channels or a disease-specific (i.e. phosphorylated) form of the receptor may represent a viable therapeutic target. Though the mechanisms regulating ion channel expression under pathological conditions are not fully known, an increased understanding of these pathways has important implications for drug development.
Hanna-Mitchell
Ann T
AT
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Birder
Lori A
LA
D058667:Adrenergic beta-3 Receptor Agonists; D001905:Botulinum Toxins / Q000627:therapeutic use; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011983:Receptors, Purinergic / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D001745:Urinary Bladder Diseases / Q000188:drug therapy / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism
D058667:Adrenergic beta-3 Receptor Agonists; D010726:Phosphodiesterase Inhibitors; D011983:Receptors, Purinergic; D050051:Transient Receptor Potential Channels; D054460:rho-Associated Kinases; D001905:Botulinum Toxins