Marthan R, Crevel H, Guénard H, Savineau J P
Laboratoire de Physiologie, Faculté de Médecine Victor Pachon, Université de Bordeaux II, France.
Respir Physiol. 1992 Nov;90(2):239-50. doi: 10.1016/0034-5687(92)90084-a.
Passive sensitization of human isolated airway smooth muscle increases contractile responses to histamine. We looked to see whether this increase was due to an alteration in the relative role of histamine H1 and H2 receptors. Human bronchial spiral strips obtained at thoracotomy were passively sensitized by incubation in serum from atopic asthmatic patients to Dermatophagoïdes pteronyssinus and control strips were incubated in serum from healthy non-allergic non-atopic subjects. We also studied spiral strips dissected from two spontaneously sensitized human lung specimens. Cumulative concentration-response curves (CCRC) to Ca2+ (10(-5) -3 x 10(-2) M) were constructed either in the presence of 10(-5) M histamine alone or in that of the combination histamine and the H2 antagonist cimetidine (10(-5) M). Unlike in the absence of histamine, Ca2+ CCRC in the presence of histamine alone were significantly shifted to the left in the passively sensitized tissues (mean EC50: 5.7 x 10(-4) M) compared to control ones (mean EC50: 9.3 x 10(-4) M, n = 6, P < 0.05). Addition of cimetidine to histamine did not alter the Ca2+ CCRC either in the control or in passively or spontaneously sensitized airway smooth muscle. These results suggest that (i) passive sensitization increases contractile response to Ca2+ of human bronchial smooth muscle in the presence of histamine; (ii) this increase is not due to a difference in the H1- vs H2-mediated response; and (iii) H2-mediated effects do not play a significant role in spontaneously sensitized human lung as both in the non-sensitized and passively sensitized lung.
人离体气道平滑肌的被动致敏会增强对组胺的收缩反应。我们探究了这种增强是否归因于组胺H1和H2受体相对作用的改变。在开胸手术时获取的人支气管螺旋条，通过在来自特应性哮喘患者的血清中孵育以使其被动致敏，致敏对象为粉尘螨，对照条则在来自健康非过敏非特应性受试者的血清中孵育。我们还研究了从两个自发致敏的人肺标本中解剖得到的螺旋条。分别在单独存在10⁻⁵ M组胺或组胺与H2拮抗剂西咪替丁（10⁻⁵ M）联合存在的情况下，构建对Ca²⁺（10⁻⁵ - 3×10⁻² M）的累积浓度 - 反应曲线（CCRC）。与不存在组胺的情况不同，在被动致敏组织中单独存在组胺时的Ca²⁺ CCRC相较于对照组织（平均EC50：9.3×10⁻⁴ M，n = 6，P < 0.05）显著左移（平均EC50：5.7×10⁻⁴ M）。在对照、被动或自发致敏的气道平滑肌中，向组胺中添加西咪替丁均未改变Ca²⁺ CCRC。这些结果表明：（i）被动致敏在有组胺存在的情况下会增强人支气管平滑肌对Ca²⁺的收缩反应；（ii）这种增强并非由于H1介导反应与H2介导反应的差异；（iii）H2介导的效应在自发致敏的人肺中不起重要作用，在未致敏和被动致敏的肺中均如此。
