Formation of prostaglandins and leukotrienes by human lung tissue in vitro after activation by the calcium ionophore A23187.
The formation of metabolites of arachidonic acid by the cyclo-oxygenase and lipoxygenase pathways were determined in human lung tissue, obtained from surgery. In this measurement the chopped tissue was incubated with the calcium ionophore A23187. Formation of metabolites from [1-14C] arachidonic acid was also determined. The metabolites were extracted, separated by HPLC and identified by measurement of the absorption spectrum at 280 nm, radioactivity, biological activity and by radioimmunoassay. 6-keto-prostaglandin F1 alpha (6-ketoPGF1 alpha), the metabolite of prostacyclin, is the cyclo-oxygenase product present in the highest amount (400 +/- 49 ng g-1), followed by PGD2 (162 +/- 59 ng g-1) thromboxane B2 (102 +/- 32 ng g-1) PGE2 (104 +/- 46 ng g-1) and PGF2 alpha (58 +/- 26 ng g-1). The amounts of the lipoxygenase products are: leukotriene B4 (LTB4), 163 +/- 100 ng g-1; LTC4, 63 +/- 31 ng g-1 and LTE4 121 +/- 34 ng g-1. From [1-14C] arachidonic acid higher amounts of the cyclooxygenase than of the lipoxygenase products were formed, with the exception of PGE2. The effects of several of these substances on the contraction of human small airway smooth muscle were measured. The contractions, induced by equivalent amounts of LTC4 and a synthetic analogue of thromboxane T X A2 were approximately one hundred times those induced by PGD2, PGF2 alpha and histamine. These results suggest that thromboxane A2 and LTC4 are the most important arachidonic acid metabolites that induce bronchoconstriction in the human lung.
Zijlstra
F J
FJ
Department of Pharmacology, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
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D000368:Aged; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000096:biosynthesis; D011457:Prostaglandins D / Q000096:biosynthesis; D013189:SRS-A / Q000096:biosynthesis; D013928:Thromboxane A2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D011457:Prostaglandins D; D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D013928:Thromboxane A2; D015230:Prostaglandin D2