Is the epithelium-derived inhibitory factor in guinea-pig trachea a prostanoid?

Abstract

To examine further the possible prostanoid involvement in the influence of the epithelium on guinea-pig tracheal smooth muscle responsiveness, we have analyzed the effects of LTD 4, methacholine and histamine on the level of airway smooth muscle tone and on the amounts of PGE 2α and PGI 2 (determined by radioimmunoassay) in the presence and absence of the epithelium. Removal of the epithelium increased the sensitivity of guinea-pig trachea to the contractile effects of LTD 4, methacholine and histamine. LTD 4 (3–100 nM), methacoline (0.1–10 μM) or histamine (0.3–30 μM) did not increase prostanoid release above control values in either the presence or absence of the epithelium. The unstimulated release of PGE 2 and PGF 2α but not PGI 2, was decreased in tissues lacking epithelium. Indomethacin (1 μM) reduced the baseline tone to a smaller extent in the absence of epithelium. In the presence but not the absence of the epithelium, indomethacin increased the sensitivity of preparations to the contractile effect of methacholine. The results support the postulate of an epithelium-derived inhibitory factor modulating guinea-pig tracheal smooth muscle responsiveness. The identity of this factor is not known but is not PGI 2 and is unlikely to be PGF 2α or PGE 2. However, the possibility remains that the basal release of PGE 2 and/or PGF 2α derived from the epithelium may markedly affect the responsiveness of guinea-pig tracheal smooth muscle. Furthermore, the epithelium is a significant source of PGE 2 and PGF 2α which may be involved in the maintenance of baseline tone.