Evidence that the histamine sensitivity and responsiveness of guinea‐pig isolated trachea are modulated by epithelial prostaglandin E2 production

Abstract

1 Guinea-pig isolated tracheal preparations in which the epithelium had been removed exhibited a greater contractile response to histamine (intact: 1.91 ± 0.12g; n = 6 and rubbed: 2.76 ± 0.15g; n = 11; P < 0.001). The histamine sensitivity (pD₂ value) of these preparations was also significantly greater (intact: 4.80 ± 0.04 and rubbed: 5.40 ± 0.08; P < 0.01). 2 Indomethacin suppressed the basal tone of both intact and rubbed preparations but was more effective in the former tissues (intact: −0.70 ± 0.14g; n = 22 and rubbed: −0.17 ± 0.05g; n = 12; P < 0.02). 3 Arachidonic acid (AA; 10 μM) suppressed the basal tone of intact tissues but contracted such preparations following indomethacin treatment (1.7 μM; 30 min). However, in rubbed tissues AA (10 μM) induced a contraction which was attenuated following indomethacin treatment. 4 Prostaglandin E₂ (PGE₂; 0.01 and 0.1 μM) suppressed the basal tone of intact preparations and always evoked contraction of rubbed tissues. Following indomethacin treatment PGE₂ (0.01 and 0.1 μM) generally evoked spasm of intact and rubbed tissues while at higher concentrations (1 μM) relaxant effects were observed. 5 Removal of the epithelium did not alter the relaxant effect of PGE₂ (pD₂ value) on histamine (50 μM)-contracted tissues (intact: 6.86 ± 0.08 and rubbed: 7.10 ± 0.3; n = 4; P > 0.1). 6 In rubbed preparations treated with indomethacin, PGE₂ (0.01 and 0.1 μM) evoked spasm. However, when added to preparations contracted with 5 μM histamine, PGE₂ always caused relaxation. 7 The release of immunoreactive PGE₂ by rubbed preparations during histamine and/or AA stimulation was significantly less than that produced by intact stimulated tissues. 8 Exogenous PGE₂ (0.01-1 μM) decreased the maximal response and sensitivity of rubbed tracheal preparations to histamine. 9 These results suggest that release of an epithelial derived cyclo-oxygenase product, namely PGE₂, may regulate basal tone, histamine response and sensitivity of the guinea-pig isolated trachea.