The Inhibitory Effect of Botulinum Toxin Type A on Rat Pyloric Smooth Muscle Contractile Response to Substance P In Vitro.
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.
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. shaoyf@lzu.edu.cn.
Yu-Feng
YF
Shao
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. xiejfan@163.com.
Jun-Fan
JF
Xie
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. renyx@lzu.edu.cn.
Yin-Xiang
YX
Ren
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. wangc2012@lzu.cn.
Can
C
Wang
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. kongxp530@163.com.|Department of Human Anatomy, School of Medicine, Hunan Normal University, 371 Tongzipo Road, Changsha 410013, China. kongxp530@163.com.
Xiang-Pan
XP
Kong
Department of Functional Examination, the 2nd Hospital of Gansu Province, Lanzhou 730000, China. zxj0547@163.com.
Xiao-Jian
XJ
Zong
Experimental Center of Medicine, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou 730000, China. fanll@lzu.edu.cn.
Lin-Lan
LL
Fan
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. houyiping@lzu.edu.cn.
Yi-Ping
YP
Hou
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D011708:Pylorus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D013373:Substance P; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; D019274:Botulinum Toxins, Type A
antagonist of neurokinin 1 receptor; botulinum toxin type A; electric field stimulation; neurokinin 1 receptor; pyloric smooth muscle contractility; rat; substance P