The Inhibitory Effect of Botulinum Toxin Type A on Rat Pyloric Smooth Muscle Contractile Response to Substance P In Vitro

Toxins (Basel). 2015 Oct 15;7(10):4143-56. doi: 10.3390/toxins7104143.


A decrease in pyloric myoelectrical activity and pyloric substance P (SP) content following intrasphincteric injection of botulinum toxin type A (BTX-A) in free move rats have been demonstrated in our previous studies. The aim of the present study was to investigate the inhibitory effect of BTX-A on rat pyloric muscle contractile response to SP in vitro and the distributions of SP and neurokinin 1 receptor (NK1R) immunoreactive (IR) cells and fibers within pylorus. After treatment with atropine, BTX-A (10 U/mL), similar to [D-Arg¹, D-Phe⁵, D-Trp(7,9), Leu(11)]-SP (APTL-SP, 1 μmol/L) which is an NK1R antagonist, decreased electric field stimulation (EFS)-induced contractile tension and frequency, whereas, subsequent administration of APTL-SP did not act on contractility. Incubation with BTX-A at 4 and 10 U/mL for 4 h respectively decreased SP (1 μmol/L)-induced contractions by 26.64% ± 5.12% and 74.92% ± 3.62%. SP-IR fibers and NK1R-IR cells both located within pylorus including mucosa and circular muscle layer. However, fewer SP-fibers were observed in pylorus treated with BTX-A (10 U/mL). In conclusion, BTX-A inhibits SP release from enteric terminals in pylorus and EFS-induced contractile responses when muscarinic cholinergic receptors are blocked by atropine. In addition, BTX-A concentration- and time-dependently directly inhibits SP-induced pyloric smooth muscle contractility.

Keywords: antagonist of neurokinin 1 receptor; botulinum toxin type A; electric field stimulation; neurokinin 1 receptor; pyloric smooth muscle contractility; rat; substance P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / pharmacology*
  • Electric Stimulation
  • In Vitro Techniques
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiopathology
  • Myoelectric Complex, Migrating / drug effects
  • Pylorus / drug effects*
  • Pylorus / metabolism
  • Pylorus / physiopathology
  • Rats, Sprague-Dawley
  • Substance P / analogs & derivatives*
  • Substance P / metabolism*
  • Substance P / pharmacology


  • Substance P
  • substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-
  • Botulinum Toxins, Type A