Endothelin-1 induces mucosal mast cell degranulation and tissue injury via ET_A receptors

The effects of endothelin-1 (ET-1) on mucosal mast cells are of special interest, since they may be an important component of the tissue response that occurs during ischaemic preconditioning or ischaemia/re-oxygenation injuries. Increasing doses of ET-1 were administered intravenously to anaesthetized rats. In a second series of experiments, animals were pretreated with the ET_A receptor antagonists BQ-610 or ETR-P1/fl peptide, or with the ET_B receptor antagonist IRL-1038. Intestinal perfusion changes were recorded, and the proportion of degranulated mast cells and the degree of mucosal damage were determined in ileal biopsies. ET-1 induced dose-dependent alterations in the haemodynamic and morphological parameters, and caused significant mast cell degranulation. These changes were inhibited significantly by pretreatment with the ET_A receptor antagonists, but not with the ET_B receptor antagonist. We conclude that a cross-talk exists between endothelial cell-derived humoral mediators and the intestinal mast cell system.