モルモット感作肺からの chemical mediator 放出におよぼす lipoxygenase 阻害剤の作用について

抄録

Leukotrienes, which are derived from arachidonic acid have similar chemical structures to prostaglandins, have recently been shown to possess most of the biological activity previously attributed to “slow reacting substance of anaphylaxis” (SRS-A). In the past two years, it has been established that the SRS-A activity is almost entirely attributable to leukotrienes C₄, D₄, and E₄ (LTC₄, LTD₄, and LTE₄). Lipoxygenese catalyzes the oxygenation of arachidonic acid and biosynthetizes leukotrienes.
The present investigation was conducted to demonstrate the effect of AA-861 and T-22083, specific inhibitors of lipoxygenase activity, on the release of chemical mediators from passively sensitized quinea pig lung tissues.
Male Hartley strain guinea pigs weighing about 200g were used as the experimental animals. The lung tissue was minced into fragments (10-20mg). The lung fragments were incubated in gamma globulin solution at 37°C for 3-4 hours bubbling with oxygen and carbon dioxde (95:5, v/v). Histamine and SRS-A released from the lung tissue by the antigen (ovalbumin) challenge were quantitated by bioassay methods.
1) The amount of histamine released from sensitized lung tissue by the challenge of antigen showed marked decrease by preincubating with AA-861 or T-22083, and the percent inhibition by AA-861 was bigger than that by T-22083.
2. The amount of SRS-A released from passively sensitized lung tissue by antigen challenge showed marked decrease by preincubation with AA-861 or T-22083, and the percent inhibition by AA-861 was bigger than that by T-22083.
The above results suggest that AA-861 and T-22083, have not only an inhibiting action on the release of SRS-A from sensitized lung tissue but also have an inhibiting action on the release of histamine, and that these drugs might become useful therapeutic agents against various anaphylactic reactions including bronchial asthma.