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Formation of prostaglandins and leukotrienes by human lung tissue in vitro after activation by the calcium ionophore A23187
Author(s) -
ZIJLSTRA F. J.,
NAAKTGEBOREN M.,
MONS H.,
VINCENT J. E.
Publication year - 1987
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1987.tb02195.x
Subject(s) - arachidonic acid , chemistry , cyclooxygenase , leukotriene , ionophore , metabolite , lipoxygenase , prostacyclin , thromboxane , calcium , prostaglandin , prostaglandin e , thromboxane b2 , thromboxane a2 , medicine , endocrinology , biochemistry , enzyme , biology , platelet , receptor , organic chemistry , asthma
. 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‐ 14 C] 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 F 1α (6‐ketoPGF 1α ), the metabolite of prostacyclin, is the cyclo‐oxygenase product present in the highest amount (400±49 ng g ‐1 ), followed by PGD 2 (162±59 ng g ‐1 ) thromboxane B 2 (102 ± 32 ng g ‐1 ) PGE 2 (104 ± 46 ng g ‐1 ) and PGF 2α (58 ± 26 ng g ‐1 ). The amounts of the lipoxygenase products are: leukotriene B 4 (LTB 4 ), 163 ± 100 ng g ‐1 ; LTC 4 , 63±31 ng g ‐1 and LTE 4 121±34 ng g ‐1 . From [1‐ 14 C] arachidonic acid higher amounts of the cyclooxygenase than of the lipoxygenase products were formed, with the exception of PGE 2 . 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 LTC 4 and a synthetic analogue of thromboxane T x A 2 were approximately one hundred times those induced by PGD 2 , PGF 2α and histamine. These results suggest that thromboxane A 2 and LTC 4 are the most important arachidonic acid metabolites that induce bronchoconstriction in the human lung.