title: Involvement of eicosanoids and macrophage-like cells in cytokine-mediated changes in rat myenteric nerves.
abstract: OBJECTIVE
  Proinflammatory cytokines alter function in enteric nerves, but little is known about underlying mechanisms. This study was designed to investigate the roles of prostanoids and of macrophage-like cells in cytokine-induced suppression of [3H]norepinephrine release from rat myenteric plexus.
  
  
  METHODS
  The release of 3H from jejunal longitudinal muscle-myenteric plexus preparations that had been loaded with [3H]norepinephrine was measured. Measurements of 3H release as well as concentrations of prostaglandin E2 and leukotriene were made in preparations exposed to interleukin 1 beta plus interleukin 6 and in the presence or absence of piroxicam, 5-lipoxygenase inhibitor MK886, cycloheximide, or cyclosporin A. An ultrastructural analysis was also performed to investigate the presence of macrophage-like cells in the myenteric plexus.
  
  
  RESULTS
  Interleukin 1 beta plus interleukin 6 suppressed 3H release and caused an increase in tissue prostaglandin E2 but not leukotriene E4. Piroxicam and cycloheximide but not MK886 attenuated the cytokine-induced increase in prostaglandin E2 and the suppression of [3H]norepinephrine release. Ultrastructural analysis showed macrophage-like cells in the plexus, and the cytokine effects were inhibited by cyclosporin A.
  
  
  CONCLUSIONS
  Prostanoids but not leukotrienes mediate the cytokine-induced suppression of norepinephrine release, and the results of this study suggest that macrophage-like cells are also involved.
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007583:Jejunum / Q000294:innervation; D015289:Leukotrienes / Q000096:biosynthesis / Q000378:metabolism; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D009130:Muscle, Smooth / Q000294:innervation; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009638:Norepinephrine / Q000378:metabolism; D010894:Piroxicam / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D002722:Chlorobenzenes
chemical_list: D003513:Cycloheximide; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D015777:Eicosanoids; D007211:Indoles; D007375:Interleukin-1; D015850:Interleukin-6; D015289:Leukotrienes; D009638:Norepinephrine; D010894:Piroxicam; D011500:Protein Synthesis Inhibitors; C060893:MK-886; D002722:Chlorobenzenes