Franconi G M, Graf P D, Lazarus S C, Nadel J A, Caughey G H
Cardiovascular Research Institute, University of California, San Francisco.
J Pharmacol Exp Ther. 1989 Mar;248(3):947-51.
Recent evidence suggests that nonadrenergic airway relaxation may be controlled by vasoactive intestinal peptide (VIP). The magnitude and duration of smooth muscle relaxation in response to VIP may be influenced by rates of peptide degradation after release from efferent peptidergic neurons. To explore the potential role of mast cell mediators in modulating neural control of airway tone, we studied the effect of the mast cell proteases tryptase and chymase on airway smooth muscle relaxation induced by VIP in ferret airway. Tracheal rings precontracted by serotonin (10(-6) M) in a muscle bath were relaxed by VIP (10(-7) M). We found that protease-rich supernatant obtained by degranulation of dog mastocytoma cells reversed VIP-induced relaxation, as did highly purified tryptase and chymase incubated with the tracheal rings. Either enzyme completely reversed the effect of VIP, but tryptase was more potent than chymase, paralleling previous test tube observations on the relative rates of VIP cleavage by the two enzymes. Inhibitors of mast cell tryptase and chymase preincubated with the supernatant or with the purified proteases prevented reversal of VIP-induced relaxation. Mast cell proteases did not reverse the tracheal relaxation caused by the nonpeptide adrenergic agonist isoproterenol. These findings show that mast cell proteases tryptase and chymase counteract the smooth muscle relaxant effects of VIP in ferret trachea and suggest a potential role for the mast cell proteases in the modulation of nonadrenergic neural control of airway tone by VIP.
最近的证据表明，非肾上腺素能气道舒张可能受血管活性肠肽（VIP）控制。从传出肽能神经元释放后，肽的降解速率可能会影响平滑肌对VIP反应的幅度和持续时间。为了探究肥大细胞介质在调节气道张力神经控制中的潜在作用，我们研究了肥大细胞蛋白酶类胰蛋白酶和糜蛋白酶对雪貂气道中VIP诱导的气道平滑肌舒张的影响。在肌肉浴中用5-羟色胺（10⁻⁶ M）预收缩的气管环可被VIP（10⁻⁷ M）舒张。我们发现，犬肥大细胞瘤细胞脱颗粒获得的富含蛋白酶的上清液可逆转VIP诱导的舒张，与气管环一起孵育的高度纯化的类胰蛋白酶和糜蛋白酶也有同样作用。两种酶均可完全逆转VIP的作用，但类胰蛋白酶比糜蛋白酶更有效，这与之前在试管中观察到的两种酶对VIP裂解的相对速率一致。与上清液或纯化蛋白酶预孵育的肥大细胞类胰蛋白酶和糜蛋白酶抑制剂可防止VIP诱导的舒张被逆转。肥大细胞蛋白酶不会逆转非肽类肾上腺素能激动剂异丙肾上腺素引起的气管舒张。这些发现表明，肥大细胞蛋白酶类胰蛋白酶和糜蛋白酶可抵消雪貂气管中VIP的平滑肌舒张作用，并提示肥大细胞蛋白酶在VIP调节非肾上腺素能神经对气道张力的控制中具有潜在作用。
