Studies On The Mechanisms Of Respiratory System Effects Of Verticinone-cholic Acid Salt

Objective: To investigate the addiction, antitussive and antiashmative mechanisms of Verticinone-cholic acid salt (Ver-CA).Methods: 1. We took naloxone urged withdrawl tests of mice for the judgment of Ver-CA's addiction. 2. Tests on citric acid-induced cough model and trachea smooth muscle (TSM) of guinea-pigs were taken for observation of Ver-CA's effects on ATP-sensitive K+ channels (KATP). 3. Tests on guinea-pig trachea smooth muscle were taken for observation of Ver-CA's antagonism effects to varieties of spasmogens.Results: 1. The jump numbers and percentage of weight decrease of mice of Ver-CA group showed no significant difference with negative control group, but were less than two positive control groups(p<0.05); the percentage of jumping animals of Ver-CA group was similar to negative control group, but obviously lower than positive control groups. 2. The inhibition percentage of cough of Ver-CA + glibenclamide group was significantly lower than that of Ver-CA + saline group (p<0.05). Ver-CA dose-dependently inhibited the contractions of TSM induced by high concentration of KCl, but did not affect the contractions induced by low concentration of KCl. 3. Ver-CA dose-dependently caused the effect-dosage curves of acetylcholine shift to the right, with a pD2'4.69, and relaxed the contraction induced by acetylcholine, with a IC50 14.1703μmol/l. Ver-CA dose-dependently caused the effect-dosage curve of 5-HT shift to the right, with a pA2 4.02, and antagonized the phaseⅠcontraction which was caused by the release of intracellular Ca2+, but did not affect the phaseⅡcontraction which was caused by the Ca2+ influx. Conclusion: 1. Ver-CA is not addictive. 2. It is not certain whether Ver-CA can activate KATP, thus the periphery antitussive effects of Ver-CA is unclear. 3. Ver-CA can antagonize TSM contraction induced by either acetylcholine or 5-HT, thus generate its antiashmative effect in two ways.