Toxins 2015, 7(10), 4143-4156; https://doi.org/10.3390/toxins7104143
The Inhibitory Effect of Botulinum Toxin Type A on Rat Pyloric Smooth Muscle Contractile Response to Substance P In Vitro
1
Department of Neuroscience, Anatomy, Histology and Embryology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou 730000, China
2
Department of Human Anatomy, School of Medicine, Hunan Normal University, 371 Tongzipo Road, Changsha 410013, China
3
Department of Functional Examination, the 2nd Hospital of Gansu Province, Lanzhou 730000, China
4
Experimental Center of Medicine, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou 730000, China
†
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Bahman Jabbari
Received: 28 July 2015 / Revised: 2 October 2015 / Accepted: 8 October 2015 / Published: 15 October 2015
(This article belongs to the Collection Botulinum Toxins on Human Pain)
Abstract
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-Trp7,9, Leu11]-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. View Full-TextKeywords:
botulinum toxin type A; substance P; electric field stimulation; neurokinin 1 receptor; antagonist of neurokinin 1 receptor; pyloric smooth muscle contractility; rat
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Shao, Y.-F.; Xie, J.-F.; Ren, Y.-X.; Wang, C.; Kong, X.-P.; Zong, X.-J.; Fan, L.-L.; Hou, Y.-P. The Inhibitory Effect of Botulinum Toxin Type A on Rat Pyloric Smooth Muscle Contractile Response to Substance P In Vitro. Toxins 2015, 7, 4143-4156.