Effect of stimulation intensity and botulinum toxin isoform on rat bladder strip contractions.
The present experiments compared the inhibitory effects of botulinum toxin A (BoNT-A) and botulinum toxin D (BoNT-D) on neurally evoked contractions of rat bladder strips. We examined the effect of fatigue (trains of 100 shocks at 20Hz every 20s for 10min) followed by non-fatigue stimulation (trains of 100 shocks at 20Hz every 100s for 20min) on the onset of effect and potency of the two toxins. For non-fatigue experiments, strips were untreated (n=4); or incubated with 1.36nM BoNT-A (n=4). During fatigue experiments, strips were untreated (n=5); or treated with either 1.36nM BoNT-A (n=6) or 0.8nM BoNT-D (n=6). In non-fatigue experiments, BoNT-A produced significant decreases in contractile area after 1h of stimulation compared to untreated strips (P<0.05). After three series of fatigue stimulation, differences in recovery amplitude and area between untreated versus BoNT-A, and untreated versus BoNT-D bladder strips, were statistically significant (P<0.05). The onset of inhibitory effect was quicker in BoNT-D-treated strips, as a significant reduction (P<0.05) in recovery of contractile area was observed after 1h of stimulation compared to both untreated and BoNT-A-treated preparations. In addition, treated (BoNT-A and BoNT-D) and untreated bladder strips responded similarly to atropine, suggesting that the effects of BoNT result from inhibition of both acetylcholine and ATP release. Our results demonstrate that BoNT-D may be a more effective agent to inhibit transmitter release from autonomic nerves of the rat lower urinary tract. Moreover, in our hands, non-fatigue stimulation is as effective as fatigue stimulation in inhibiting bladder strip contractions.
Smith
Christopher P
CP
Scott Department of Urology, Baylor College of Medicine, One Baylor Plaza, Alkek Building, N720, Houston, TX 77030, USA.
Boone
Timothy B
TB
de Groat
William C
WC
Chancellor
Michael B
MB
Somogyi
George T
GT
D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D005221:Fatigue / Q000503:physiopathology; D005260:Female; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D020033:Protein Isoforms / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D018726:Anti-Dyskinesia Agents; D018727:Muscarinic Antagonists; D020033:Protein Isoforms; D001285:Atropine; D001905:Botulinum Toxins