Quercetin Stimulates Na+/K+/2Cl− Cotransport via PTK-Dependent Mechanisms in Human Airway Epithelium

• DOI: 10.1165/rcmb.2008-0338oc
• Publication Date: 2009-02-28T02:51:18Z
• Authors: Junji Asano; Naomi Niisato; Ken-ichi Nakajima; Hiroaki Miyazaki; Makoto Yasuda; Yoshinobu Iwasaki; Takemitsu Hama; Kenji Dejima; Yasuo Hisa; Yoshinori Marunaka
• Keywords: 0303 health sciences; Brefeldin A; Ion Transport; Valinomycin; Sodium-Potassium-Chloride Symporters; Epithelial Cells; Respiratory Mucosa; Protein-Tyrosine Kinases; Tyrphostins; Cell Line; ErbB Receptors; 03 medical and health sciences; Chlorides; Sodium Potassium Chloride Symporter Inhibitors; Quinazolines; Humans; Solute Carrier Family 12, Member 2; Quercetin; Enzyme Inhibitors; Bumetanide; Signal Transduction

We investigated regulatory mechanisms of Cl(-) secretion playing an essential role in the maintenance surface fluid human airway epithelial Calu-3 cells. The present study reports that quercetin (a flavonoid) stimulated bumetanide-sensitive with reduction apical conductance, suggesting stimulates by activating entry step across basolateral membrane through Na(+)/K(+)/2Cl(-) cotransporter (NKCC1). To clarify mechanism stimulating NKCC1 quercetin, we verified involvement protein kinase (PK)A, PKC, tyrosine (PTK), and cytosolic Ca(2+)-dependent pathways. A PKA inhibitor (PKI-14-22 amide), a PKC (Gö 6983) or Ca(2+) chelating agent did not affect quercetin-stimulated secretion. On other hand, PTK (AG18) significantly diminished stimulatory action on without inhibitory effects PTK-mediated pathway is involved quercetin. was suppressed brefeldin (BFA, vesicular transport from ER to Golgi), BFA-sensitive observed presence epidermal growth factor receptor (EGFR) (AG1478), causing EGFR kinase-mediated translocation NKC1-activating However, density increased but elevated activity NKCC1. These observations indicate via NKCC1-activating kinase-dependent pathway.