The Inhibitory Effect of Botulinum Toxin Type A on Rat Pyloric Smooth Muscle Contractile Response to Substance P In Vitro
Yu-Feng Shao,
Jun-Fan Xie,
Yin-Xiang Ren,
Can Wang,
Xiang-Pan Kong,
Xiao-Jian Zong,
Lin-Lan Fan,
Yi-Ping Hou
Affiliations
Yu-Feng 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
Jun-Fan 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
Yin-Xiang 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
Can 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
Xiang-Pan Kong
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
Xiao-Jian Zong
Department of Functional Examination, the 2nd Hospital of Gansu Province, Lanzhou 730000, China
Lin-Lan Fan
Experimental Center of Medicine, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou 730000, China
Yi-Ping Hou
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
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.
