Minette P A, Barnes P J
Department of Thoracic Medicine, Cardiothoracic Institute, London, United Kingdom.
J Appl Physiol (1985). 1988 Jun;64(6):2532-7. doi: 10.1152/jappl.1988.64.6.2532.
We have investigated whether prejunctional inhibitory muscarinic receptors ("autoreceptors") exist on cholinergic nerves in human airways in vitro and whether guinea pig trachea provides a good model for further pharmacological characterization of these receptors. Pilocarpine was used as a selective agonist and gallamine as a selective antagonist of these autoreceptors. Acetylcholine (ACh) release from postganglionic cholinergic nerves was elicited by electrical field stimulation (EFS) (40 V, 0.5 ms, 32 Hz). In human bronchi, pilocarpine inhibited the contractile response to EFS in a dose-related fashion; the dose inhibiting 50% of the control contraction was 2.2 +/- 0.4 x 10(-7) (SE) M (n = 22), and the inhibition was 96% at 3 x 10(-5) M. The inhibitory effects of pilocarpine were antagonized by gallamine in a dose-related fashion. The results were qualitatively the same in the guinea pig. Gallamine significantly enhanced the contractile response to EFS in the guinea pig, whereas pirenzepine failed to do so, which suggests that M2-receptors are involved. We conclude that prejunctional muscarinic receptors that inhibit ACh release are present on cholinergic nerves in human airways and that guinea pig trachea is a good model for further pharmacological characterization of these receptors, which appear to belong to the M2-subtype.
我们研究了人呼吸道胆碱能神经上是否存在节前抑制性毒蕈碱受体（“自身受体”），以及豚鼠气管是否可作为进一步对这些受体进行药理学特性研究的良好模型。毛果芸香碱用作这些自身受体的选择性激动剂，加拉明用作选择性拮抗剂。通过电场刺激（EFS）（40V，0.5ms，32Hz）诱发节后胆碱能神经释放乙酰胆碱（ACh）。在人支气管中，毛果芸香碱以剂量相关方式抑制对EFS的收缩反应；抑制对照收缩50%的剂量为2.2±0.4×10⁻⁷（SE）M（n = 22），在3×10⁻⁵M时抑制率为96%。毛果芸香碱的抑制作用被加拉明以剂量相关方式拮抗。在豚鼠中结果在定性上相同。加拉明显著增强豚鼠对EFS的收缩反应，而哌仑西平则无此作用，这表明涉及M2受体。我们得出结论，人呼吸道胆碱能神经上存在抑制ACh释放的节前毒蕈碱受体，豚鼠气管是进一步对这些似乎属于M2亚型的受体进行药理学特性研究的良好模型。
