Platelet-activating factor-acether-induced relaxation of guinea pig airway muscle: role of prostaglandin E2 and the epithelium

Abstract

A fixed concentration of paf-acether (platelet-activating factor; 4 microM) relaxed isolated guinea pig tracheal preparations which had been contracted with histamine (50 microM), serotonin (1 microM) or leukotriene D4 (0.1 microM). The relaxations were approximately 43, 100 and 57%, respectively. We did not observe any relaxant effect of paf-acether (4 microM) in tissues contracted with acetylcholine (50 microM). Both lyso paf-acether (10 microM) and bovine serum albumin (25 micrograms/ml) were without effect on histamine-contracted preparations. In the presence of indomethacin (1.7 microM; 30 min) or aspirin (0.1 mM; 30 min) the relaxant effect of paf-acether (4 microM) in tissues contracted with histamine was significantly reduced to approximately 10 and 12%, respectively. When paf-acether (4 microM) was added to histamine-contracted tracheal preparations in the presence of noradrenaline (0.1 microM) or prostaglandin E2 (PGE2, 10 nM) the relaxations were 62 and 82%, respectively. Noradrenaline and PGE2 alone had only a slight relaxant effect in these tissues (7 and 14%, respectively). In the presence of indomethacin (1.7 microM) the synergistic effect of paf-acether and PGE2 was still observed. The basal production of PGE2 in isolated guinea pig tracheal preparations was 4.6 +/- 1.4 pg/mg of tissue. In the presence of paf-acether (4 microM) increased levels of this prostanoid were detected (11.2 +/- 2.4 pg/mg of tissue). Isolated guinea pig tracheal preparations when contracted with histamine released PGE2 (17.6 +/- 4.1 pg/mg of tissue). In the presence of histamine and paf-acether there was a significant increase in detectable levels of PGE2 (48.6 +/- 13.2 pg/mg of tissue).(ABSTRACT TRUNCATED AT 250 WORDS)