Belvisi M G, Stretton C D, Verleden G M, Ledingham S J, Yacoub M H, Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
J Appl Physiol (1985). 1992 Mar;72(3):1096-100. doi: 10.1152/jappl.1992.72.3.1096.
Opioids reduce the cholinergic responses to electrical field stimulation (EFS) in guinea pig and canine airways by a prejunctional effect. We determined whether a similar effect operates in human airways in vitro. [D-Ala2-NMePhe4-Gly-ol5]enkephalin (DAMGO) (10(-8)-10(-6) M), a selective mu-opioid receptor agonist, inhibited the response to EFS in a dose- and frequency-dependent manner. DAMGO (10(-6) M) produced 86% inhibition at 0.5 Hz and 38% inhibition at 4 Hz, but at 32 Hz there was no significant inhibition. Another selective mu-opioid receptor agonist H-Tyr-D-Arg-Gly-Phe(4-NO2)-Pro-NH2 diacetate (BW 443C) also inhibited responses to EFS, producing 57.7% inhibition at 4 Hz at a concentration of 10(-6) M. The inhibitory effect on EFS was blocked by the opioid receptor antagonist naloxone (10(-5) M), indicating that opioid receptors are involved. DAMGO (10(-6) M) had no effect on the contractile response to exogenous acetylcholine, indicating a prejunctional effect. We conclude that mu-opioid agonists inhibit cholinergic neurotransmission in human airways in vitro, and this could have therapeutic potential in the treatment of airway disease.
阿片类药物通过节前效应降低豚鼠和犬气道对电场刺激（EFS）的胆碱能反应。我们确定了在体外人气道中是否存在类似效应。[D-丙氨酸2-N-甲基苯丙氨酸4-甘氨醇5]脑啡肽（DAMGO）（10^(-8)-10^(-6) M），一种选择性μ-阿片受体激动剂，以剂量和频率依赖性方式抑制对EFS的反应。DAMGO（10^(-6) M）在0.5 Hz时产生86%的抑制，在4 Hz时产生38%的抑制，但在32 Hz时无明显抑制。另一种选择性μ-阿片受体激动剂H-酪氨酸-D-精氨酸-甘氨酸-苯丙氨酸（4-硝基）-脯氨酰胺二乙酸盐（BW 443C）也抑制对EFS的反应，在10^(-6) M浓度下于4 Hz时产生57.7%的抑制。对EFS的抑制作用被阿片受体拮抗剂纳洛酮（10^(-5) M）阻断，表明阿片受体参与其中。DAMGO（10^(-6) M）对外源性乙酰胆碱的收缩反应无影响，表明存在节前效应。我们得出结论，μ-阿片激动剂在体外抑制人气道中的胆碱能神经传递，这在气道疾病治疗中可能具有治疗潜力。
