title: 2-APB and capsazepine-induced Ca2+ influx stimulates clathrin-dependent endocytosis in alveolar epithelial cells.
abstract: Calcium as a second messenger influences many cellular and physiological processes. In lung, alveolar type II (ATII) cells sense mechanical stress and respond by Ca(2+) dependent release of surfactant, which is essential for respiratory function. Nevertheless, Ca(2+) signaling mechanisms in these cells--in particular Ca(2+) entry pathways are still poorly understood. Herein, we investigated pharmacological properties of non-voltage-gated Ca(2+) channel modulators in ATII and NCI-H441 cells and demonstrate that 2-Aminoethoxydiphenyl-borinate (2-APB) and capsazepine (CPZ) activate Ca(2+) entry with pharmacologically distinguishable components. Surprisingly, 2-APB and CPZ activated clathrin dependent endocytosis in ATII and NCI-H441 cells, which was dependent on Ca(2+) entry. The internalized material accumulated in non-acidic granules distinct from surfactant containing lamellar bodies (LB). LB exocytosis was not observed under these conditions. Our study demonstrates that 2-APB/CPZ induces Ca(2+) entry which unlike ATP- or stretch-induced Ca(2+) entry in ATII cells does not activate exocytosis but an opposing endocytotic mechanism.
authors.affiliation: Institute of General Physiology, University of Ulm, Ulm, Germany.
authors.forename: Shariq M
authors.initials: SM
authors.lastname: Usmani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fois
authors.forename: Susanne
authors.initials: S
authors.lastname: Albrecht
authors.forename: Sonja
authors.initials: S
authors.lastname: von Aulock
authors.forename: Paul
authors.initials: P
authors.lastname: Dietl
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Wittekindt
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001896:Boron Compounds; D002966:Clathrin; C109986:2-aminoethoxydiphenyl borate; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium