The effect of removing the epithelium on the responses of the guinea‐pig isolated trachea (GPT) to bradykinin (BK) and prostaglandin E2 (PGE2) was investigated.
BK (3 pmol–10 nmol) induced dose‐related relaxations of the intact (with epithelium), and contracted the rubbed (without epithelium) preparation of GPT. Similar responses were also obtained with PGE2 (0.3–3.0 nmol).
Indomethacin (1.4 μm) modified the BK‐induced response of intact GPT, from a relaxation to a contraction, but inhibited the BK‐induced contraction of the rubbed GPT.
There was a significant increase in PGE2 release from the intact GPT following stimulation with BK.
Removal of the epithelium from the GPT significantly reduced both basal and BK‐induced generation of PGE2.
The induction of tone in the rubbed GPT by addition of acetylcholine (ACh) caused BK and PGE2 (0.3 nmol–3 nmol) to produce relaxations of the tissue.
Salbutamol (10−8 m‐10−6 m) reduced the relaxations induced by BK on intact GPT, in a concentration‐dependent manner.
These results suggest that both tone and an epithelial‐dependent cyclo‐oxygenase mechanism are important in modulating BK‐induced responses of GPT.
Leukotriene C4 (LTC4), LTD4, slow‐reacting substance of anaphylaxis (SRS‐A) (from guinea‐pig lung), bradykinin (Bk) and arachidonic acid (AA) release thromboxane A2 (TxA2) and prostaglandin‐like materials from guinea‐pig isolated perfused lungs.
Release of TxA2 induced by LTC4 and LTD4 is inhibited by a thromboxane synthetase inhibitor, imidazole (2.9 mm).
Mepacrine (200 μm), a phospholipase inhibitor, inhibits release of TxA2 and prostaglandin‐like materials caused by SRS‐A and Bk but not that due to exogenous AA
Leukotrienes B4, C4 and D4 are approximately equipotent in inducing dose‐related contractions of guinea‐pig parenchymal strips (GPPs).
Leukotriene‐induced contractions of GPPs are greatly inhibited by imidazole (2.9 mm), carbox‐yheptylimidazole (24 μm) and mepacrine (400 μm).
FPL 55712 (1.9 μm), the SRS‐A antagonist, blocks contractions of GPPs induced by LTC4 and LTD4 but not those due to LTB4 or Bk.
Tachyphylaxis to LTB4 occurs in GPPs but not to LTC4 or LTD4.
These results suggest that in guinea‐pig lung in vitro, LTB4, LTC4 and LTD4 activate a phospholipase with subsequent generation of cyclo‐oxygenase products of which TxA2 plays an important role.
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