Endothelins promote egg albumin-induced intestinal anaphylaxis in rats.
OBJECTIVE
The basic mechanisms of food allergies are still unknown. The aims of this study were to investigate whether endothelins (ETs) in the intestinal mucosa are involved in the pathogenesis of intestinal anaphylaxis.


METHODS
Sprague-Dawley rats were sensitized to chicken egg albumin (EA) by intraperitoneal injection. Fourteen days after sensitization, EA was administered in the jejunal segments to induce intestinal anaphylaxis. Net water outflux and histamine release into loops and serum concentrations of rat mast cell protease II (RMCP-II) were determined. ET-1 and ET-3 concentrations in the jejunal mucosa were determined, and expression of the corresponding messenger RNAs was examined by competitive polymerase chain reaction.


RESULTS
In sensitized animals, challenge with intraluminal antigen caused a significant increase in net water outflux and histamine release together with an elevation of serum RMCP-II concentrations. Mucosal concentrations of ET-1 and ET-3 and expression of their messenger RNAs were significantly increased in sensitized animals after EA challenge. Treatment with an ETA-receptor antagonist, but not an ETB-receptor antagonist, attenuated the increase in net water outflux, histamine release, and serum RMCP-II concentrations in rats with EA-induced intestinal anaphylaxis.


CONCLUSIONS
Release of ETs in the intestinal mucosa increased in sensitized animals after EA challenge. ETs may play a significant role in the development of intestinal anaphylaxis via an ETA receptor.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
T
T
Shigematsu
S
S
Miura
M
M
Hirokawa
R
R
Hokari
H
H
Higuchi
Y
Y
Tsuzuki
H
H
Kimura
R C
RC
Nakatsumi
H
H
Serizawa
H
H
Saito
H
H
Ishii
D000418:Albumins / Q000276:immunology*; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D000077300:Bosentan; D002460:Cell Line; D002645:Chickens; D004531:Eggs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D019334:Endothelin-3 / Q000502:physiology*; D006632:Histamine / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology; D007422:Intestines / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D000418:Albumins; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D013449:Sulfonamides; C086539:BQ 788; D006632:Histamine; D012697:Serine Endopeptidases; C057818:cytotoxic T lymphocyte-specific serine protease; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)