Effects of Pilocarpine on Isolated Rat Trachea

Pilocarpine對於離體老鼠氣管之作用

邱逢翔(Feng-Shiang Chiu) ； 劉紹正(Shao-Cheng Liu) ； 王興萬(Hsing-Won Wang)

《台灣耳鼻喉頭頸外科雜誌》 52卷1期 (2017/03) Pp. 15-22

https://doi.org/10.6286/2017.52.1.15

摘要

BACKGROUND: Pilocarpine is a non-selective muscarinic agonist; oral pilocarpine is used for the treatment of xerostomia, and topical pilocarpine, for relief from glaucoma. Direct application of this drug on oral cavity and throat is assumed an alternative for asthmatic patients with xerostomia, contraindicated for systemic administration of pilocarpine. How topical use of pilocarpine affects the trachea remains unknown. This study aimed to determine the effects of pilocarpine on the rat trachea in vitro. METHODS: We tested the effectiveness of pilocarpine on isolated rat trachea submersed in Krebs solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following parameters were assessed to determine the effects of pilocarpine on the tracheal muscle: (i) tracheal smooth muscle resting tension; (ii) contraction caused by parasympathetic mimetic of 10-6 M methacholine; and (iii) the effect of the drug on electrically induced tracheal smooth muscle contractions. RESULTS: Increasing concentrations of pilocarpine alone had a minimal effect on the basal tension of the trachea. However, pilocarpine induced significant relaxation of methacholine-challenged tracheal strips at a concentration up to 10^(-5) M or 10^(-4) M. This drug also inhibited the electrical field stimulation-induced spike contraction at a concentration of 10^(-4) M. CONCLUSIONS: High concentrations of pilocarpine may directly antagonize the cholinergic effect of methacholine and inhibit the electric field stimulation induced airway contraction.

關鍵字

trachea ； asthma ； in vitro study ； pilocarpine ； xerostomia

並列摘要

背景：毛果芸香鹼(pilocarpine)為一種非選擇性的蕈鹼類受器促效劑(muscarinic agonist)。臨床上可口服毛果芸香鹼藥物治療因放射線治療或乾燥症導致的口乾，也可局部滴注於眼睛以治療青光眼。針對氣喘患者的口乾症，局部使用毛果芸香鹼於患者口腔或喉嚨經查閱文獻為一有效的方式，然是否會造成如同口服藥物般引起系統性副作用、如氣管張力改變等則尚不清楚。本實驗的目的在於利用老鼠的離體氣管模組，初步探討毛果芸香鹼直接作用於氣管後的效應。方法：吾人使用切下來的老鼠氣管、浸潤於Krebs溶液並兩端固定給予基礎張力，實驗主要分三組：(1)由低到高依序將不同濃度的毛果芸香鹼加入溶液裡；(2)先於溶液裡加入10^(-6) M乙醯甲膽鹼(methacholine)使氣管收縮，再由低到高依序加入不同濃度的毛果芸香鹼；(3)以電刺激使氣管收縮，再由低到高依序加入不同濃度的毛果芸香鹼；上述實驗在給予藥物後記錄其氣管張力變化。結果：單獨添加毛果芸香鹼對於氣管張力幾乎沒有改變。當氣管因乙醯甲膽鹼(methacholine)收縮後，較高濃度的毛果芸香鹼(10^(-5) M及10^(-4) M)會降低氣管的張力、使其舒張。高濃度(10^(-4)M)的毛果芸香鹼亦會抑制氣管因電刺激造成的張力增加。結論：高濃度的毛果芸香鹼可拮抗乙醯甲膽鹼(methacholine)的膽鹼性收縮，同時也抑制電場刺激導致的氣管張力收縮。

並列關鍵字

trachea ； asthma ； in vitro study ； pilocarpine ； xerostomia（氣管 ； 氣喘 ； 離體試驗 ； 毛果芸香鹼 ； 口乾）