Imipramine inhibits Cl- secretion by desensitization of beta-adrenergic receptors in Calu-3 human airway cells

Recent investigations have found that tetracyclic antidepressants like imip ramine (IMP) have high-affinity sites not only in brain but also in mammali an lung. In the present study, we examined the effects of IMP on the Cl- se cretion produced by isoproterenol (ISP), a beta-adrenergic receptor (beta-A R) agonist, in Calu-3 human airway cells. ISP applied in the basolateral so lution generated a sustained short-circuit current that was abolished by di phenylamine-2-carboxylate, a Cl- channel blocker, IMP (0.01-1 mM) applied i n the apical or basolateral solution for 30 min significantly inhibited the ISP-induced responses in a concentration-dependent manner, and the inhibit ory effects of this drug were remarkable when applied from the apical rathe r than the basolateral side. ISP-induced responses were mimicked by forskol in- and 8-bromo-cyclic AMP-induced ones, but which were insensitive to IRIP . These results indicate that IMP desensitizes the beta-AR on the basolater al membrane from the cytosolic side in Calu-3 cells. (C) 2000 Academic Pres s.