Platelet-activating factor and prostaglandin E2 impair esophageal ACh release in experimental esophagitis.
ACh is a neurotransmitter in cat esophageal circular muscle, as atropine nearly abolishes contraction of in vitro circular muscle strips in response to electric field stimulation (EFS) (5, 12). Experimental esophagitis reduced EFS- but not ACh-induced contraction of esophageal circular muscle, suggesting that esophagitis impairs neurotransmitter release. Because IL-1beta and IL-6 are produced in esophagitis and reproduce these changes in normal esophageal muscle (12), we examined the role of IL-1beta and IL-6 in this motor dysfunction. IL-1beta, IL-6 (12), H2O2, PGE2, and platelet-activating factor (PAF) were elevated in esophagitis specimens. Normal muscle incubated (2 h) in IL-1beta and IL-6 had increases in H2O2, PGE2, and PAF levels. H2O2 contributed to increased PGE2 and PAF, as the increase was partially (60-80%) reversed by the H2O2 scavenger catalase. EFS-induced [3H]ACh release from muscle strips significantly (42%) decreased in esophagitis and after 2 h incubation in PGE2 and in PAF C-16. Similarly, EFS-induced but not ACh-induced muscle contraction decreased in esophagitis and after incubation in PGE2 and PAF C-16. Finally, in normal muscle strips treated with IL-1beta electrical field stimulation (EFS)-induced contraction was partially restored by indomethacin or by the PAF antagonist CV3988 and was completely restored by the combination of CV3988 and indomethacin, whereas in strips treated with IL-6, EFS-induced contraction was partially restored by the PAF antagonist CV3988 and not affected by indomethacin. We conclude that IL-1beta-induced production of H2O2 causes formation of PGE2 and PAF that inhibit ACh release from esophageal cholinergic neurons without affecting ACh-induced contraction of esophageal circular muscle. IL-6 causes production of H2O2, PAF, and other unidentified inflammatory mediators.
Cheng
Ling
L
Rhode Island Hospital, Providence, RI, USA.
Cao
Weibiao
W
Fiocchi
Claudio
C
Behar
Jose
J
Biancani
Piero
P
Harnett
Karen M
KM
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002415:Cats; D015232:Dinoprostone / Q000502:physiology*; D004941:Esophagitis / Q000503:physiopathology*; D004947:Esophagus / Q000502:physiology; D007249:Inflammation; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth; D010972:Platelet Activating Factor / Q000502:physiology*; D017382:Reactive Oxygen Species
D007375:Interleukin-1; D015850:Interleukin-6; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D015232:Dinoprostone; D000109:Acetylcholine