REDUCTION IN THE BIOELECTRIC PROPERTIES OF SWINE TRACHEAL SUBMUCOSAL GLAND-CELLS IN CULTURE AFTER DAILY SHORT-TERM EXPOSURE TO COCAINE

Chronic use of cocaine has been associated with respiratory complicati ons. In this study, we investigated the effects of daily short-term co caine exposure on epithelial bioelectric properties and chloride secre tion in response to secretagogues in primary culture of swine tracheal submucosal gland cells grown on microporous inserts. Cell cultures ex posed continuously to cocaine for 24 h or intermittently for 30 min da ily for up to 3 consecutive days, resulted in a concentration-dependen t reduction in transwell voltage and transepithelial resistance. Cocai ne (300 mu M) treatment for 24 h decreased the voltage and resistance by 87 and 75%, respectively. The voltage and resistance were also subs tantially decreased after 3 days of intermittent cocaine (10-30 mu M) 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 exposur e did not change the decreases in short-circuit current caused by amil oride (10 mu M), but reduced the increases in short-circuit current in duced by acetylcholine and isoproterenol. After 3 days of intermittent cocaine (30 mu M) exposure, the maximal acetylcholine and isoproteren ol responses were reduced by 67 and 71%, respectively. Therefore, coca ine exposure continuously for 24 h or intermittently for 30 min daily for up to 3 days decreased basal transepithelial voltage as well as re sistance and reduced the responses to cholinergic and beta-adrenocepto r agonists. These results suggest that alterations in epithelial funct ion can occur even after daily transient cocaine exposure. (C) 1997 El sevier Science B.V.