Inhibition of lung surfactant secretion from alveolar type II cells and annexin II tetramer-mediated membrane fusion by phenothiazines

Archives of Biochemistry and Biophysics
L LiuUn-Jin Zimmerman

Abstract

We investigated the effects of phenothiazines on lung surfactant secretion from rat alveolar epithelial type II cells and on annexin II tetramer (Anx IIt)-mediated membrane fusion. Trifluoperazine and promethazine inhibited ATP-stimulated phosphatidylcholine (PC) secretion from type II cells in a dose-dependent manner. Concentrations that cause 50% inhibition (IC50) were approximately 3 and 25 microM for trifluoperazine and promethazine, respectively. Promethazine also inhibited PC secretion of type II cells stimulated by other secretagogues, including calcium ionophore A23187, phorbol 12-myristate 13-acetate, and terbutaline that are known to stimulate PC secretion via different signal transduction pathways. Since we have recently determined that Anx IIt is involved in PC secretion of type II cells, we examined whether phenothiazines influence Anx IIt's activity. Trifluoperazine and promethazine inhibited Anx IIt's ability to aggregate phosphatidylserine (PS) liposomes, to fuse PS/phosphatidylethanolamine (PE) liposomes, and to fuse PS/PE liposomes with lamellar bodies. These results suggest a relationship between lung surfactant secretion and Anx IIt-mediated membrane fusion.

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Citations

Mar 12, 2008·The Journal of Biological Chemistry·Deming GouLin Liu
Feb 16, 2005·Annual Review of Physiology·Paul Dietl, Thomas Haller
Aug 30, 2003·American Journal of Respiratory Cell and Molecular Biology·Michael A ShultzAlan R Buckpitt
Mar 31, 2015·Biochimica Et Biophysica Acta·Ralf ZarbockMatthias Griese
Aug 30, 2002·European Journal of Biochemistry·Lin LiuDavid M Terrian
Mar 28, 2002·Physiological Reviews·Volker Gerke, Stephen E Moss
Aug 26, 1998·Biochimica Et Biophysica Acta·A Szewczyk, S Pikuła
Jul 30, 2021·The Journal of Biological Chemistry·Anne Sofie Busk HeitmannJesper Nylandsted

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