Tudoric N, Coon R L, Bosnjak Z J
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.
Pulm Pharmacol. 1994 Oct;7(5):343-7. doi: 10.1006/pulp.1994.1040.
Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic construction of guinea-pig tracheal smooth muscle. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on constriction induced by the non-immunological mast cell degranulator-compound 48/80. Phosphoramidon produced significant leftward shift of the compound 48/80 concentration-response curve with corresponding decrease in the EC50 value from 51 (28-80) micrograms/ml to 42 (20-72) micrograms/ml. When added during the compound 48/80-induced constriction, phosphoramidon significantly increased the magnitude of this constriction by 69.7% after 30 min, and 78.9% after 45 min. Phosphoramidon was ineffective in tracheal rings from tachykinin-depleted guinea pigs. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl, 10 microM) and leukotriene receptor antagonist (ICI 198.615, 5 microM) significantly diminished the contractile response to compound 48/80 and prevented a phosphoramidon-dependent increase of this constriction. These results suggest that compound 48/80 induces the release of tachykinins by the stimulatory activity of histamine and leukotrienes. Anaphylactic release of tachykinins would therefore not depend directly on the antigen-antibody reaction.
我们之前的研究表明，抑制中性内肽酶（一种可降解速激肽的酶）会增强豚鼠气管平滑肌的过敏性收缩。为了进一步研究这一现象，我们检测了中性内肽酶抑制剂磷酰胺素对非免疫性肥大细胞脱颗粒剂——化合物48/80诱导的收缩的影响。磷酰胺素使化合物48/80浓度 - 反应曲线显著左移，相应地，半数有效浓度（EC50）值从51（28 - 80）微克/毫升降至42（20 - 72）微克/毫升。在化合物48/80诱导的收缩过程中加入磷酰胺素，30分钟后该收缩幅度显著增加69.7%，45分钟后增加78.9%。磷酰胺素对速激肽耗竭的豚鼠的气管环无效。气管环与H1组胺受体拮抗剂（盐酸苯海拉明，10微摩尔）和白三烯受体拮抗剂（ICI 198.615，5微摩尔）共同孵育，可显著减弱对化合物48/80的收缩反应，并阻止磷酰胺素依赖性的收缩增强。这些结果表明，化合物48/80通过组胺和白三烯的刺激活性诱导速激肽释放。因此，速激肽的过敏性释放不会直接依赖于抗原 - 抗体反应。
