Mitchell H W, Hau H, Denborough M A
Eur J Pharmacol. 1979 Aug 15;57(4):399-406. doi: 10.1016/0014-2999(79)90502-8.
The mechanisms involved in the anti-asthmatic action of combined bronchodilator therapy was studied by determining the effects of combined salbutamol and theophylline on anaphylactic contractions, histamine release, prostaglandin (PG)F2 ALha release, cyclic 3',5'-adenosine monophosphate (c-AMP) and smooth muscle tone in guinea-pig peripheral airways in vitro. Combined, salbutamol (3 X 10(=8) M) and theophylline (3 X 10(-4) M) markedly inhibited anaphylactic contractions (85.8%) in lung strips. The inhibition of anaphylactic contractions was significantly greater than inhibition of histamine and PGF2 alpha-induced contractions. Histamine release was reduced by 66.1% but PGF2 alpha was not significantly altered. Increased c-AMP was observed with combined salbutamol (3 X 10(-8) M) and theophylline (3 X 10(-4) M) in the absence of antigen. The combined effect of salbutamol and theophylline was always greater than the sum of their individual effects. The results demonstrate that in peripheral airways theophylline potentiates the action of salbutamol both directly via smooth muscle relaxation and indirectly via inhibition in mediator release.
通过测定沙丁胺醇与茶碱联用对豚鼠外周气道过敏性收缩、组胺释放、前列腺素（PG）F2α释放、环磷腺苷（c-AMP）及平滑肌张力的影响，研究了联合支气管扩张剂治疗哮喘作用的机制。在体外实验中，沙丁胺醇（3×10⁻⁸M）与茶碱（3×10⁻⁴M）联用可显著抑制肺条中的过敏性收缩（85.8%）。对过敏性收缩的抑制作用明显大于对组胺和PGF2α诱导收缩的抑制作用。组胺释放减少了66.1%，但PGF2α没有显著变化。在无抗原的情况下，沙丁胺醇（3×10⁻⁸M）与茶碱（3×10⁻⁴M）联用可使c-AMP增加。沙丁胺醇与茶碱的联合作用总是大于它们各自作用的总和。结果表明，在外周气道中，茶碱可通过直接使平滑肌舒张和间接抑制介质释放来增强沙丁胺醇的作用。
