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

Toxins

Yu-Feng Shao²  Jun-Fan Xie²  Yin-Xiang Ren²  Can Wang²  Xiang-Pan Kong²  Xiao-Jian Zong³  Lin-Lan Fan¹  Yi-Ping Hou² 

[1] Experimental Center of Medicine, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou 730000, China; E-Mail:;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; E-Mails:;Department of Functional Examination, the 2nd Hospital of Gansu Province, Lanzhou 730000, China; E-Mail:

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

DOI  :  10.3390/toxins7104143

来源: mdpi

【 摘 要 】

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, 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.