The urothelium in overactive bladder: passive bystander or active participant?
The urothelium was once purported to be a passive membrane. However, a growing body of evidence indicates that the urothelium actively participates in sensory functions, expressing various receptors and ion channels, as well as releasing neurotransmitters in response to stimuli. Vanilloid receptors, P2X3 purinergic receptors, adenosine triphosphate, nitric oxide, and acetylcholine have been implicated in urothelial-neuronal interactions. Substances released from urothelial cells can alter the excitability of bladder afferent nerves acutely and chronically; these observations appear to be of particular importance in chronic bladder conditions and in the aging bladder. Evidence suggests that the involvement of the muscarinic receptor in bladder function extends beyond detrusor contractility and into afferent sensory functioning. These observations have significant implications for a more complete understanding of the effects of currently used drugs on these sensory mechanisms and for identifying potential targets for pharmacologic intervention in bladder disorders.
de Groat
William C
WC
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. degroat@server.pharm.pitt.edu
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006801:Humans; D051379:Mice; D011955:Receptors, Drug / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058477:Receptors, Purinergic P2X3; D020886:Somatosensory Disorders / Q000503:physiopathology; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000502:physiology*; D001745:Urinary Bladder Diseases / Q000503:physiopathology*; D019459:Urothelium / Q000033:anatomy & histology / Q000502:physiology*
C546407:P2RX3 protein, human; C546409:P2rx3 protein, mouse; D011955:Receptors, Drug; D011976:Receptors, Muscarinic; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate