Drug Insight: biological effects of botulinum toxin A in the lower urinary tract.
Botulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.
Chancellor
Michael B
MB
Department of Urology, William Beaumont Hospital in Royal Oak, MI 8073, USA. chancellormb@gmail.com
Fowler
Clare J
CJ
Apostolidis
Apostolos
A
de Groat
William C
WC
Smith
Christopher P
CP
Somogyi
George T
GT
Aoki
K Roger
KR
D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D006801:Humans; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology; D014551:Urinary Tract / Q000187:drug effects* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects*
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A