Abstract
In order to examine the modulation of leukotriene (LT) release, the PAF-acether-mediated stimulation of these compounds in rat lung was studied. Release of LTC 4, LTD 4 and LTE 4 in both perfused and chopped lung preparations was measured using HPLC and radioimmunoassay. Pre-incubation or pre-infusion of the tissue with indomethacin and PGE 2 was conducted to investigate the effect of cyclooxygenase inhibitors and products on the lipoxygenase pathway. In addition, the effects of LT levels of pre-incubation with vasoactive intenstinal polypeptide (VIP) in chopped lung were observed. In perfused rat lung, indomethacin reduced the levels of LTC 4 relative to LTD 4 as measured in the first 2 min after stimulation of the lung by PAF-acether. Chopped lung preparations, incubated for 15 min. exhibited higher levels of LTC 4 and LTD 4 in indomethacin-treated samples, this increases being effectively reversed by PGE 2. In the VIP pre-incubation experiments clear inhibition of peptido -leukotriene synthesis was observed, with no LTC 4 and only low levels of LTD 4 and LTE 4 observed in VIP-incubated samples. In preliminary experiments using rabbit C5a des arg and PAF-acether on rabbit lung parenchyma strips to stimulaet LT release, disodium cromoglycate pre-incubation was observed to inhibit this release. Inhibition of the 5-lipoxygenase pathway of PGE 2 is supported by these experiments. VIP appears to act as an inhibitor of LTC 4 and LTD 4 biosynthesis or release in this model. Too little is known that peptidergic actions to postulate a mechanism by which a neuroendocrine peptide exerts control of release of arachidonate metabolites; however, VIP is associated with muscarinic stimulation (1) and has been found in mast cells (2).
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