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.
Highlights
Botulinum toxin (BTX) is produced from the bacterium clostridium botulinum
Intrasphincteric injection of botulinum toxin type A (BTX-A) has been recently proposed as an alternative to treat pyloric dysfunction or pylorospasm [14] and demonstrated that it induces a decrease in pyloric myoelectrical activity and pyloric substance P (SP) content in free move rats [16]
When BTX-A instead of APTL-SP was added following atropine, its inhibitory effect on electric field stimulation (EFS)-induced contractile responses was similar to APTL-SP, and APTL-SP addition did not influence contractile responses to EFS again (Figure 2)
Summary
Botulinum toxin (BTX) is produced from the bacterium clostridium botulinum. It is well investigated that the major target of BTX is the cholinergic nerve ending of neuromuscular junctions in skeletal muscles, where the inhibition of acetylcholine (ACh) release results in neuromuscular blockade and paralysis [4,5]. BTX-A has been successfully used in the treatment of voluntary muscle contraction disorders such as strabismus, dystonia, and tremors [4,6,7,8,9]. In smooth muscles, an injection of BTX-A into pylorus in patients with gastroparesis might relax the pylorus and facilitate gastric emptying. BTX-A appears to reduce cholinergic transmission by inhibiting ACh release, as shown in vitro [13,14]
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