Rabe K F, Giembycz M A, Dent G, Perkins R S, Evans P, Barnes P J
Department of Thoracic Medicine, Royal Brompton National Heart and Lung Institute, London, UK.
Eur J Pharmacol. 1993 Feb 9;231(2):305-8. doi: 10.1016/0014-2999(93)90466-u.
The ability of the long-acting beta-adrenoceptor agonists eformoterol and salmeterol to inhibit leukotriene (LT) B4 (100 nM; approximately EC70)-induced hydrogen peroxide (H2O2) generation by guinea-pig peritoneal eosinophils was investigated and compared with salbutamol. Eformoterol and salbutamol produced a concentration-dependent inhibition of LTB4-induced H2O2 generation with pIC50 values of 6.22 and > 5.0 respectively. The inhibitory effect eformoterol was mediated through an interaction with beta-adrenoceptors for it was antagonised by propranolol with an affinity (7.21) that was independent of antagonist concentration (100 nM and 1 microM). In contrast, salmeterol (1 nM to 10 microM) failed to inhibit H2O2 generation at any concentration examined irrespective of the pre-incubation time (0, 0.25, 0.5, 1, 2, 15 or 30 min). Salmeterol did, however, competitively antagonise (slope of Schild plot = 0.91) the inhibition of H2O2 generation induced by eformoterol with a pA2 of 5.9. Possible explanations for the lack of inhibitory effect of salmeterol on LTB4-induced respiratory burst are advanced and critically discussed.
研究了长效β-肾上腺素能受体激动剂福莫特罗和沙美特罗抑制豚鼠腹腔嗜酸性粒细胞中白三烯（LT）B4（100 nM；约为EC70）诱导的过氧化氢（H2O2）生成的能力，并与沙丁胺醇进行了比较。福莫特罗和沙丁胺醇对LTB4诱导的H2O2生成产生浓度依赖性抑制，pIC50值分别为6.22和>5.0。福莫特罗的抑制作用是通过与β-肾上腺素能受体相互作用介导的，因为普萘洛尔能拮抗其作用，亲和力（7.21）与拮抗剂浓度（100 nM和1 μM）无关。相比之下，无论预孵育时间（0、0.25、0.5、1、2、15或30分钟）如何，沙美特罗（1 nM至10 μM）在任何检测浓度下均未能抑制H2O2生成。然而，沙美特罗确实能竞争性拮抗（Schild图斜率=0.91）福莫特罗诱导的H2O2生成抑制作用，pA2为5.9。本文提出并批判性地讨论了沙美特罗对LTB4诱导的呼吸爆发缺乏抑制作用的可能解释。
