Imipramine inhibits Cl(-) secretion by desensitization of beta-adrenergic receptors in calu-3 human airway cells.
Recent investigations have found that tetracyclic antidepressants like imipramine (IMP) have high-affinity sites not only in brain but also in mammalian lung. In the present study, we examined the effects of IMP on the Cl(-) secretion produced by isoproterenol (ISP), a beta-adrenergic receptor (beta-AR) agonist, in Calu-3 human airway cells. ISP applied in the basolateral solution generated a sustained short-circuit current that was abolished by diphenylamine-2-carboxylate, a Cl(-) channel blocker. IMP (0.01-1 mM) applied in the apical or basolateral solution for 30 min significantly inhibited the ISP-induced responses in a concentration-dependent manner, and the inhibitory effects of this drug were remarkable when applied from the apical rather than the basolateral side. ISP-induced responses were mimicked by forskolin- and 8-bromo-cyclic AMP-induced ones, but which were insensitive to IMP. These results indicate that IMP desensitizes the beta-AR on the basolateral membrane from the cytosolic side in Calu-3 cells.
Second Division (Respiratory Division), First Department of Physiology, School of Medicine, Nagoya University, Tsurumai-cho, Showa-ku, Nagoya, 466, Japan.
Y
Y
Mizuno
Y
Y
Ito
M
M
Aoyama
H
H
Kume
S
S
Nakayama
K
K
Yamaki
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D007099:Imipramine / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012137:Respiratory System / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D018118:Chloride Channels; D002712:Chlorides; D011943:Receptors, Adrenergic, beta; D062367:ortho-Aminobenzoates; C001209:fenamic acid; D007099:Imipramine