Removal of guinea pig bronchial and tracheal epithelium potentiates the contractions to leukotrienes and histamine

Abstract

Mechanical removal of guinea pig bronchial and tracheal epithelium by rubbing the luminal surface resulted in a significant dose-dependent increase of the contractile responses to leukotrienes (LT) A4, C4, D4, E4 and histamine. Histological examinations were made to confirm either the presence or the absence of the epithelium and the integrity of underlying tissues. The contractions elicited by the high doses of LTA4, C4, D4 and E4 were potentiated by 2.7, 3.2, 1.9 and 4.5 fold respectively on trachea and by 2.1, 1.9, 2.3 and 1.9 fold respectively on upper bronchi in the absence of the epithelial layer. Histamine and LTD4 induced the release of prostaglandins (PG) E2 and I2 by intact or epithelium-denuded tracheal and bronchial rings. Diphenhydramine (4.0 x 10(-6) M) inhibited significantly the release of relaxant prostanoids induced by histamine, whereas the compound MK-571 (1.0 x 10(-6) M) did not inhibit leukotriene D4-stimulated release. These antagonists inhibited tracheal and bronchial contractions in either the absence or presence of epithelium. Indomethacin (2.8 x 10(-6) M) enhanced the myotropic activities of histamine and LTD4 on the trachea and bronchi deprived of their epithelial layer. These results suggest that PGE2 and I2 are major components of the epithelium-derived relaxing factor. Our results suggest however that underlying tissues are also responsible for the release of these relaxant prostanoids.