Cocaine and tracheal epithelial function: effects on short circuit current and neurotransmitter receptors

After snorting crystalline cocaine, the nasal and airway mucosa will be exposed to high concentrations of this drug. We have examined the actions of mucosal and serosal cocaine application on the basal short circuit current (Isc) and the changes in Isc (delta Isc) induced by acetylcholine (ACh) and isoproterenol (ISO) across swine tracheal epithelium. Cocaine displacement of muscarinic receptor and beta adrenoceptor radioligands was also examined. Cocaine at low, less than 1 mM, concentrations induced basal Isc to increase in some tissues by 9 to 10 microA in some preparations it induced only a decrease in basal Isc. The maximal decrease was 15 to 20 microA in these preparations. In all tissues 14 mM cocaine decreased basal Isc. The IC50 for the cocaine inhibition of Isc was 3 +/- 0.9 mM after mucosal application. Mucosal cocaine (3 mM) did not affect the actions of mucosal amiloride, an epithelial sodium channel blocker (IC50 = 0.6 +/- .1 microM, control; 1.5 +/- 0.3 microM, in the presence of 3 mM cocaine) or serosal tetraethylammonium, a potassium channel blocker. However, cocaine altered the response of the tissue to ACh and ISO. Cocaine (14 mM) applied mucosally reduced the maximal delta Isc induced by ACh (serosal) to 34 +/- 14% of control. By contrast, serosal cocaine (3 mM) caused a parallel shift to the right in the concentration-response relationships for ACh- and ISO-induced increases in Isc (EC50 increased by approximately 6.3 and approximately 2.5 times, respectively) but did not reduce the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)