Actions of cysteinyl leukotrienes in the enteric nervous system of guinea-pig stomach and small intestine.
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 C(4), leukotriene D(4) or leukotriene E(4) 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 CysLT(1) 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 alpha-pentyl-3-(2-quinolinylmethoxy)-benzenemethanol (REV 5901), nor the dual CysLT(1)/CysLT(2) 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 (CysLT(1) and CysLT(2) receptors) and may represent a new receptor subtype.
Liu
Sumei
S
Department of Physiology and Cell Biology, The Ohio State University, College of Medicine and Public Health, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
Hu
Hong Zhen
HZ
Gao
Chuanyun
C
Gao
Na
N
Wang
Guodu
G
Wang
Xiyu
X
Gao
Xiang
X
Xia
Yun
Y
Wood
Jackie D
JD
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D003545:Cysteine / Q000494:pharmacology*; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D000098:Acetophenones; C071435:BAY u9773; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011422:Propionates; D011804:Quinolines; D013189:SRS-A; D013777:Tetrazoles; C112381:cysteinyl-leukotriene; C049740:alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; C059141:verlukast; C044660:LY 171883; D003545:Cysteine