Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury

The purpose of this paper was to simultaneously examine changes in urothelial ATP and NO release in normal and spinal cord injured animals as well as in spinal cord injured animals treated with botulinum toxin type A (BoNT-A). Furthermore we correlated changes in transmitter release with functional...

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Bibliographic Details
Published in:Neurochemistry international 2008-05, Vol.52 (6), p.1068-1075
Main Authors: Smith, Christopher P., Gangitano, David A., Munoz, Alvaro, Salas, Nilson A., Boone, Timothy B., Aoki, K. Roger, Francis, Joseph, Somogyi, George T.
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
ATP
Biological and medical sciences
Bladder
Botulinum toxin
Botulinum Toxins, Type A - pharmacology
Botulinum Toxins, Type A - therapeutic use
Chronic Disease
Disease Models, Animal
Female
Fundamental and applied biological sciences. Psychology
Hypogastric Plexus - drug effects
Hypogastric Plexus - physiopathology
Hypotonic Solutions - pharmacology
Muscle Contraction - drug effects
Muscle Contraction - physiology
Muscle, Smooth - drug effects
Muscle, Smooth - innervation
Muscle, Smooth - physiopathology
Neural Inhibition - drug effects
Neural Inhibition - physiology
Neuromuscular Agents - pharmacology
Neurotransmitter Agents - metabolism
Neurotransmitter Agents - secretion
Nitric oxide
Nitric Oxide - metabolism
Parasympathetic Nervous System - drug effects
Parasympathetic Nervous System - physiopathology
Rats
Spinal Cord Injuries - complications
Spinal cord injury
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Urinary Bladder - drug effects
Urinary Bladder - innervation
Urinary Bladder - physiopathology
Urinary Bladder, Neurogenic - drug therapy
Urinary Bladder, Neurogenic - metabolism
Urinary Bladder, Neurogenic - physiopathology
Urothelium
Urothelium - drug effects
Urothelium - metabolism
Urothelium - physiopathology
Vertebrates: nervous system and sense organs
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Summary:The purpose of this paper was to simultaneously examine changes in urothelial ATP and NO release in normal and spinal cord injured animals as well as in spinal cord injured animals treated with botulinum toxin type A (BoNT-A). Furthermore we correlated changes in transmitter release with functional changes in bladder contraction frequency, and determined the effects of BoNT-A on bladder efferent nerve function. Normal and spinal cord injured rat bladders were injected on day 0 with either vehicle (saline containing bovine serum albumin) or BoNT-A. On day 2, in vitro neurotransmitter release and bladder strip contractility studies as well as in vivo cystometrographic studies were conducted. Resting ATP release was significantly enhanced following spinal cord injury (i.e. 57% increase, p < 0.05) and was unaffected by BoNT-A treatment. SCI increased hypoosmotic evoked urothelial ATP release by 377% ( p < 0.05). BoNT-A treatment reduced evoked ATP release in SCI bladders by 83% ( p < 0.05). In contrast, hypoosmotic stimulation induced NO release was significantly inhibited following SCI (i.e. 50%, p < 0.05) but recovered in SCI rats treated with BoNT-A (i.e. 195% increase in NO release in SCI-BTX-treated rats compared to SCI controls, p < 0.01). Changes in urothelial transmitter release coincided with a significant decrease in non-voiding bladder contraction frequency (i.e. 71%, p < 0.05) in SCI-BTX rats compared to SCI rats. While no difference was measured between neurally evoked contractile amplitude between SCI and SCI-BTX animals, atropine (1 μM) inhibited contractile amplitude to a greater extent (i.e. 76%, p < 0.05) in the SCI-BTX group compared to the SCI group. We hypothesize that alterations in the ratio of excitatory (i.e. ATP) and inhibitory (i.e. NO) urothelial transmitters promote bladder hyperactivity in rat bladders following SCI that can be reversed, to a large extent, by treatment with BoNT-A.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2007.11.006