Effect of tetracosahexaenoic acid on the content and release of histamine, and eicosanoid production in MC/9 mouse mast cell.
6,9,12,15,18,21-Tetracosahexaenoic acid (24:6n-3) was isolated from a brittle star, Ophiura sarsi Lütken, at >95% purity to evaluate its physiological functions. The effects of 24:6n-3 on the production of leukotriene (LT)-related compounds such as LTB4, LTC4 and 5-hydroxyeicosatetraenoic acid, and the accumulation and release of histamine in an MC/9 mouse mast cell line were studied. We found that 24:6n-3 could inhibit the antigen-stimulated production of LT-related compounds as well as other n-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), which are major n-3 PUFA in fish oils; 24:6n-3 was also shown to reduce the histamine content in MC/9 cells at 25 microM (27% reduction from the control), and the effect was diminished with increase of the fatty acid concentration (up to 100 microM). These two n-3 PUFA, 20:5n-3 and 22:6n-3, also reduced the histamine content (16 and 20% reduction at 25 microM, respectively), whereas arachidonic acid (20:4n-6) increased it (18% increase at 25 microM). Spontaneous- and antigen-induced release of histamine was not influenced with these PUFA (at 25 microM). Ionophore-stimulated release of histamine was suppressed by the PUFA (13, 9, 15, and 11% reduction with 20:4n-6, 20:5n-3, 22:6n-3, and 24:6n-3, respectively). The patterns of the effects of 24:6n-3 on the synthesis of eicosanoids and histamine content were more similar to those of 22:6n-3 than 20:5n-3. From these results, 24:6n-3 can be expected to have anti-inflammatory activity and antiallergic activities similar to those of 22:6n-3.
Ishihara
K
K
National Research Institute of Fisheries Science, MAFF, Yokohama, Japan. hplc@nrifs.affrc.go.jp
Murata
M
M
Kaneniwa
M
M
Saito
H
H
Shinohara
K
K
Maeda-Yamamoto
M
M
Kawasaki
K
K
Ooizumi
T
T
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004447:Echinodermata / Q000737:chemistry; D015777:Eicosanoids / Q000096:biosynthesis*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice
D000941:Antigens; D015777:Eicosanoids; D015525:Fatty Acids, Omega-3; D007476:Ionophores; D004281:Docosahexaenoic Acids; C099831:tetracosahexaenoic acid