Botulinum toxin type a inhibits calcitonin gene-related peptide release from isolated rat bladder.
OBJECTIVE
Increasing evidence suggests that sensory nerve dysfunction may underlie several urological disorders, including interstitial cystitis and sensory urgency. We determined the effect of botulinum toxin type A (Allergan, Irvine, California) on baseline and chemically evoked release of the sensory neuropeptide, calcitonin gene-related peptide in an isolated bladder preparation.


METHODS
Whole rat bladders were incubated in a series of tissue baths containing physiological salt solution. Following bladder equilibration in PSS sequential incubation was performed and this sample was used to measure baseline CGRP release. To evoke CGRP release tissue was subsequently incubated in PSS containing capsaicin (30 nM) and adenosine triphosphate (10 microM). To measure the effect of BTX-A on baseline and evoked CGRP release bladders were incubated for 6 hours in an organ bath containing BTX-A (50 microM) or vehicle prior to bladder equilibration. CGRP release was determined by radioimmunoassay.


RESULTS
Mean baseline release of CGRP +/- SEM was 346 +/- 44 pg/gm. Adenosine triphosphate/capsaicin application increased CGRP release by 75% over baseline (606 +/- 98 pg/gm, p < 0.005). BTX-A application resulted in a 19% decrease in baseline release of CGRP, although this difference did not achieve statistical significance. BTX-A application significantly decreased evoked CGRP by 62% vs control (606 +/- 98 vs 229 +/- 21 pg/gm, p < 0.005).


CONCLUSIONS
BTX-A application inhibits the evoked release of CGRP from afferent nerve terminals in isolated rat bladder. This finding suggests a potential clinical benefit of BTX-A for the treatment of interstitial cystitis or sensory urgency.
Rapp
David E
DE
Section of Urology, Department of Surgery, University of Chicago Hospitals, Chicago, Illinois, USA. derapp@yahoo.com
Turk
Katherine W
KW
Bales
Gregory T
GT
Cook
Sean P
SP
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009465:Neuromuscular Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000378:metabolism*
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A; D015740:Calcitonin Gene-Related Peptide