Chan_1997_Eur.J.Pharmacol_334_281

Chronic use of cocaine has been associated with respiratory complications. In this study, we investigated the effects of daily short-term cocaine exposure on epithelial bioelectric properties and chloride secretion in response to secretagogues in primary culture of swine tracheal submucosal gland cells grown on microporous inserts. Cell cultures exposed continuously to cocaine for 24 h or intermittently for 30 min daily for up to 3 consecutive days, resulted in a concentration-dependent reduction in transwell voltage and transepithelial resistance. Cocaine (300 microM) treatment for 24 h decreased the voltage and resistance by 87 and 75%, respectively. The voltage and resistance were also substantially decreased after 3 days of intermittent cocaine (10-30 microM) exposure. Cocaine exposure protocols used here did not enhance lactate dehydrogenase (LDH) release. Chloride secretion was measured as short-circuit current utilizing Ussing chamber methodology. Cocaine exposure did not change the decreases in short-circuit current caused by amiloride (10 microM), but reduced the increases in short-circuit current induced by acetylcholine and isoproterenol. After 3 days of intermittent cocaine (30 microM) exposure, the maximal acetylcholine and isoproterenol responses were reduced by 67 and 71%, respectively. Therefore, cocaine exposure continuously for 24 h or intermittently for 30 min daily for up to 3 days decreased basal transepithelial voltage as well as resistance and reduced the responses to cholinergic and beta-adrenoceptor agonists. These results suggest that alterations in epithelial function can occur even after daily transient cocaine exposure.