Stenton G R, Lau H Y
Department of Pharmacology, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Inflamm Res. 1996 Oct;45(10):508-12. doi: 10.1007/BF02311087.
It has been reported that the loop diuretic frusemide can prevent exercise induced asthma, and that this effect may be due to the inhibition of mast cells in the airway. By using various mast cell secretagogues which increase intracellular calcium via different routes, this study attempted to elucidate the mechanism of the mast cell stabilizing action of frusemide. As well as confirming that immunologically induced histamine release from rat peritoneal mast cells was dose dependently inhibited by frusemide (10(-3) - 10(-5) M), the present study has extended the observation to histamine release induced by compound 48/80. The inhibitory potency was however less in the case of compound 48/80 induced release. Frusemide induced inhibition by the two secretagogues was decreased by drug preincubation. In contrast, histamine release induced by ionophore A23187 and thapsigargin was not inhibited by frusemide. The prototype antiallergic compound disodium cromoglycate (DSCG) demonstrated a similar specificity pattern against the various secretagogues. Another loop diuretic, bumetanide, did not show the same results as frusemide on rat peritoneal mast cell degranulation. Hence it is concluded that frusemide does not inhibit immunological activation of mast cells via its diuretic Na+/K+/Cl- co-transporter capacity. Instead, it protects mast cells in a similar manner to DSCG.
据报道，袢利尿剂速尿可预防运动诱发的哮喘，且该作用可能是由于其对气道中肥大细胞的抑制作用。本研究通过使用各种肥大细胞促分泌剂，这些促分泌剂通过不同途径增加细胞内钙，试图阐明速尿稳定肥大细胞作用的机制。除了证实速尿（10⁻³ - 10⁻⁵ M）能剂量依赖性地抑制大鼠腹膜肥大细胞经免疫诱导的组胺释放外，本研究还将观察扩展至化合物48/80诱导的组胺释放。然而，在化合物48/80诱导释放的情况下，抑制效力较低。药物预孵育可降低速尿对这两种促分泌剂诱导的抑制作用。相反，离子载体A23187和毒胡萝卜素诱导的组胺释放不受速尿抑制。原型抗过敏化合物色甘酸钠（DSCG）对各种促分泌剂表现出类似的特异性模式。另一种袢利尿剂布美他尼在大鼠腹膜肥大细胞脱颗粒方面未表现出与速尿相同的结果。因此得出结论，速尿并非通过其利尿的Na⁺/K⁺/Cl⁻共转运能力抑制肥大细胞的免疫激活。相反，它以与DSCG类似的方式保护肥大细胞。
