Gardiner P J, Copas J L, Elliott R D, Collier H O
Prostaglandins. 1978 Feb;15(2):303-15. doi: 10.1016/0090-6980(78)90170-3.
A novel test was developed to measure the tracheobronchial irritant activity of inhaled prostaglandins. Conscious restrained cats were challenged with separate aerosols of PGE1, PGF2alpha, acetylcholine or isoprenaline. All of the aerosols except isoprenaline caused coughing in a concentration related manner. Tolerance developed very quickly to the tracheobronchial irritation and lasted 1-2 days for PGE1 and less than 1 day for PGF2alpha and acetylcholine. When a 3 day interval between each aerosol challenge was used, PGF2alpha was approximately 700 times more potent than acetylcholine as a tracheobronchial irritant. The highest PGE1 aerosol concentration (500microgram/ml) also caused sedation, diarrhoea and salivation. This test probably provides a useful method for evaluating the tracheobronchial irritant activity of potential prostaglandin bronchodilator analogues and for investigating the mechanism of action of prostaglandin induced tracheobronchial irritancy.
开发了一种新的测试方法来测量吸入前列腺素的气管支气管刺激活性。对清醒受限的猫分别给予前列腺素E1、前列腺素F2α、乙酰胆碱或异丙肾上腺素气雾剂进行刺激。除异丙肾上腺素外,所有气雾剂均以浓度相关的方式引起咳嗽。对气管支气管刺激的耐受性发展非常迅速,前列腺素E1持续1 - 2天,前列腺素F2α和乙酰胆碱持续不到1天。当每次气雾剂刺激之间间隔3天时,作为气管支气管刺激剂,前列腺素F2α的效力约为乙酰胆碱的700倍。最高浓度的前列腺素E1气雾剂(500微克/毫升)还会引起镇静、腹泻和流涎。该测试可能为评估潜在前列腺素支气管扩张剂类似物的气管支气管刺激活性以及研究前列腺素诱导的气管支气管刺激的作用机制提供一种有用的方法。