Basic Pharmacology of Botulinum Toxin in the Lower Urinary Tract

Alex Tong-Long Lin

《慈濟醫學雜誌》 19卷3期 (2007/09) Pp. 109-114

並列摘要

Neurotransmitters formed in the cytosol of presynaptic nerveendings 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 synaptic 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 pro-tease activity. Once inside the cytosol, the light chain is released to cleave the specific component of SNARE protein responsible for transmitter exocytosis. 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 substanceP 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 neurotransmitters, 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 tobe around 3000U. 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 asaminoglycosides, should not be used concurrently. Decreased detrusor contractilityis 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 catheterization after BoNT administration.

並列關鍵字

Botulinum toxin ； Pharmacology ； Prostate ； Urethra ； Urinary bladder