Tachyphylaxis in 12-0-tetradecanoylphorbol acetate- and arachidonic acid-induced ear edema.
Tachyphylaxis in 12-0-tetradecanoylphorbol acetate- and arachidonic acid-induced ear edema.
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DOI：
10.1111/1523-1747.ep12531048
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
J. Young;B. Wagner;D. A. Spires
中科院分区：
文献类型：
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作者：
J. Young;B. Wagner;D. A. Spires
12-0-十四烷基佛波醇醋酸酯(TPA)应用于小鼠耳朵，迅速引起肿胀，在6小时后最大，但在24小时后基本消退。(这与许多炎症因素不同，后者会导致持续数天的长时间浮肿。)在16-24小时重新应用TPA不会引起第二次水肿性反应，尽管红斑明显增多。花生四烯酸(AA)涂在小鼠耳朵上(4毫克)会引起更快的水肿，在1小时时最大，6小时后基本消退。在3-24小时重新使用AA也不会引起第二次水肿性反应，尽管红斑也会增加。用AA预处理耳朵可抑制随后应用TPA的水肿反应，而TPA预处理可适度抑制AA的后续反应。TPA引起的水肿可被萘普生等药物延缓，后者是AA环氧合酶的抑制剂。相反，AA引起的水肿只能被既抑制环氧合酶又抑制脂氧合酶的药物，如苯尼酮所抑制。这些数据表明，水肿症是AA代谢的环氧合酶和脂氧合酶途径产物相互作用的结果。继发性水肿反应的缺乏似乎与TPA或AA不能重新诱导血管通透性有关。这种效应是AA和TPA所特有的；对二甲苯或蒽啉的反应不受TPA或AA预处理的影响。据推测，观察到的快速止血作用涉及AA的脂氧合酶代谢产物。
12-0-Tetradecanoylphorbol acetate (TPA) applied to mouse ears rapidly induces an edema which is maximal by 6 hr but has substantially waned by 24 hr. (This is in contrast to many inflammatory agents that cause a prolonged edema lasting many days.) Reapplication of TPA at 16-24 hr will not provoke a second edematous response although increased erythema is evident. Arachidonic acid (AA) applied to mouse ears (4 mg) provokes an even more rapid edema which is maximal at 1 hr and has substantially waned by 6 hr. Reapplication of AA at 3-24 hr also will not provoke a second edematous response although, again, increased erythema does result. Pretreatment of ears with AA results in inhibition of the edema response to subsequent application of TPA, and TPA pretreatment moderately inhibits a subsequent response to AA. TPA-induced edema can be delayed by agents such as naproxen, an inhibitor of AA cyclooxygenase. In contrast, AA-induced edema is inhibited only by agents, such as phenidone, that inhibit both cyclooxygenase and lipoxygenase. The data suggest that the edemas result from interaction of the products of the cyclooxygenase and lipoxygenase pathways of AA metabolism. The lack of secondary edema response appears to be related to the inability of TPA or AA to reinduce vascular permeability. The effect is specific to AA and TPA; responses to xylene or anthralin are unaffected by TPA or AA pretreatment. It is postulated that the tachyphylactic effects observed involve lipoxygenase metabolites of AA.