Epithelium selectively controls hypersensitization of the response of smooth muscle to leukotriene D4 by endogenous prostanoid(s) in guinea-pig trachea.

The effect of epithelium removal on the sensitivity of smooth muscle to carbachol and leukotriene D4 (LTD4) was investigated in guinea-pig isolated tracheal preparations untreated and treated with a cyclooxygenase inhibitor, flurbiprofen (1 mumol/l). The pD2 value of carbachol was not changed by epithelium removal or by flurbiprofen-treatment, alone or in combination. On the other hand, the pD2 of LTD4 was higher in the tracheal strips without epithelium than in the intact preparations. In preparations devoid of epithelium, the pD2 value of LTD4 was decreased by treatment with flurbiprofen, suggesting that the sensitivity of the smooth muscle (namely, epithelium-free preparations) to LTD4 is enhanced by intramurally produced excitatory prostaglandin(s) [PG(s)]. However, in intact preparations with epithelium, no such sensitized response to LTD4 was observed. After flurbiprofen-treatment, in the continued presence of prostaglandin F2 alpha (PGF2 alpha, 200 nmol/l), the sensitivity to LTD4 was partially recovered in the epithelium-free preparations, but not in the intact ones. These results suggest that epithelium diminishes the sensitizing effect of intramural excitatory PG(s) on responsiveness of tracheal smooth muscle to LTD4, possible via a non-prostanoid substance(s).