Actions of cysteinyl leukotrienes in the enteric nervous system of guinea-pig stomach and small intestine

Sumei Liu, Hong Zhen Hu, Chuanyun Gao, Na Gao, Guodu Wang, Xiyu Wang, Xiang Gao, Yun Xia, Jackie D. Wood*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Conventional intracellular microelectrodes, neuronal tracer injection techniques and immunohistochemistry were used to study the actions of cysteinyl leukotrienes (CysLTs) on electrical and synaptic behavior of enteric neurons in guinea-pig stomach and small intestine. Bath application of leukotriene C4, leukotriene D4 or leukotriene E4 evoked a slowly activating depolarizing response in most of the myenteric and submucous plexus neurons in the small intestine while no effect was observed in gastric neurons. The depolarization evoked by cysteinyl leukotrienes in intestinal neurons was associated with increased input resistance and enhanced excitability. Suppression of hyperpolarizing after-potentials occurred in AH type neurons. The depolarizing action of cysteinyl leukotrienes was resistant to tetrodotoxin and cyclooxygenase inhibitors. Neither the CysLT1 receptor antagonists (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-dimethylamino)-3- oxopropyl]thio]methyl]thio]-propanoic acid (MK 571), 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl}-ethanone (LY 171883) and α-pentyl-3-(2-quinolinylmethoxy)-benzenemethanol (REV 5901), nor the dual CysLT1/CysLT2 receptor antagonist 6(R)-(4′-carboxyphenylthio)-5(S)-hydroxy-7(E),9(E),11(Z),14(Z)- eicosatetraenoic acid (BAY u9773) significantly altered the depolarizing action of the cysteinyl leukotrienes. Neurotransmission was unaffected by the cysteinyl leukotrienes. The results suggested involvement of cysteinyl leukotrienes in enteric immuno-neural communication through excitatory actions on enteric neurons. The receptor mediating these effects was distinct from currently recognized cysteinyl leukotriene receptor subtypes (CysLT1 and CysLT2 receptors) and may represent a new receptor subtype.

Original languageEnglish
Pages (from-to)27-39
Number of pages13
JournalEuropean Journal of Pharmacology
Volume459
Issue number1
DOIs
Publication statusPublished - 10 Jan 2003
Externally publishedYes

Keywords

  • Enteric nervous system
  • Immune system
  • Inflammation
  • Intestine
  • Leukotriene
  • Myenteric plexus
  • Stomach
  • Submucosal plexus

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