Tzu Chi Medical Journal
Volume 19, Issue 3 , Pages 109-114, September 2007

Basic Pharmacology of Botulinum Toxin in the Lower Urinary Tract

  • Alex Tong-Long Lin

      Affiliations

    • Corresponding Author InformationCorresponding author. Department of Urology, School of Medicine, National Yang Ming University, 155, Section 2, Linong Street, Taipei, Taiwan

Department of Urology, School of Medicine, National Yang Ming University, Taipei, Taiwan

Received 1 February 2007; received in revised form 9 April 2007; accepted 23 April 2007.

Article Outline

Abstract 

Neurotransmitters formed in the cytosol of presynaptic nerve endings are enclosed in transport vesicles, which are then transported toward plasma membrane. Through interaction with SNARE proteins, transport vesicles fuse with plasma membrane to release neurotransmitters into the syn-aptic space. SNARE proteins are targets of botulinum toxins (BoNTs) and tetanus toxin. All types of BoNTs consist of a heavy chain and a light polypeptide joined by a disulfide bond. The light chain possesses protease activity. Once inside the cytosol, the light chain is released to cleave the specific component of SNARE protein responsible for transmitter exo-cytosis. Type A and E cleave to SNAP-25. Cleavage of SNARE protein prevents exocytosis of neurotransmitters, resulting in chemo-denervation. BoNT is known to inhibit the release of acetylcholine from cholinergic nerve terminals in the neuromuscular junctions of striated muscle. BoNT/A has been found to reduce the release of norepinephrine from the urethra. The release of CGRP and substance P is also found to be inhibited by BoNT. Stimulated release of ATP, a mediator for nociception of urinary bladder, from urothelial cells of cyclophosphamide-induced inflammatory rat bladders was significantly reduced by BoNT/A. Release of some neuro-transmitters, including neuropeptide Y and nitric oxide, is not affected by BoNTs. BoNTs might influence the presentation of membrane receptor. BoNT/A has been found to reduce the expression of adrenergic receptor in rat prostate. Higher dose of BoNT/A might cleave the SNARE protein responsible for receptor trafficking, with a resultant reduction in receptor presentation on plasma membrane. Lethal BoNT dose for humans is unknown, but referencing data derived from animal research, one would suspect a LD50 of BoNT/A for a 70-kg human to be around 3000 U. Botulism-like side effects are prone to occur in patients with neurological disorder. Serious systemic side effects from BoNT/A injection into the lower urinary tract are not common. Only a few cases of generalized weakness have been reported. Active UTI and known hypersensitivity to BoNTs prohibit BoNT application. Drugs affecting neuromuscular transmission, such as aminoglycosides, should not be used concurrently. Decreased detrusor contractility is expected following bladder injection of BoNT. Patients with significant bladder outlet obstruction should be informed of the possibility of urinary retention with a need for intermittent catheteri-zation after BoNT administration.

Keywords:  Botulinum toxin , Pharmacology , Prostate , Urethra , Urinary bladder

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PII: S1016-3190(10)60002-X

doi:10.1016/S1016-3190(10)60002-X

Tzu Chi Medical Journal
Volume 19, Issue 3 , Pages 109-114, September 2007

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