© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Involvement of myosin light-chain kinase in chloride-sensitive Ca2+ influx in porcine aortic endothelial cells
aDepartment of Internal Medicine III, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan
bDepartment of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan
* Corresponding author. Tel.: +81-53-435-2384; fax: +81-53-435-2384 hwat{at}hama-med.ac.jp
Objectives: This study was designed to investigate the involvement of myosin light-chain kinase (MLCK) in bradykinin- and thapsigargin-induced changes in intracellular Cl– and Ca2+ concentrations ([Cl–]i; [Ca2+]i) in porcine aortic endothelial cells. Methods: Using the fluorescent probes N-ethoxycarbonylmethyl-6-methoxyquinolinium bromide (MQAE) and fura-2/AM, the effects of different MLCK inhibitors on bradykinin- and thapsigargin-induced changes in [Cl–]i and [Ca2+]i were assessed. Results: Bradykinin and thapsigargin significantly decreased the MQAE fluorescence intensity, which indicates increased [Cl–]i; these changes were reversed by removal of extracellular chloride (Cl–o) and were significantly inhibited by Cl–-channel inhibitor N-phenylanthranilic acid but not by Na+–K+–Cl– cotransport inhibitor furosemide. Pretreatment with ML-9 and wortmannin, two different selective inhibitors of MLCK, significantly reduced these changes in a dose-dependent manner. The inhibitory effects of ML-9 and wortmannin on the Cl– responses were not significantly different and were not additive. Bradykinin and thapsigargin provoked large increases in [Ca2+]i, which were significantly diminished by removal of Cl–o and by pretreatment with the Cl–-channel inhibitor N-phenylanthranilic acid. Conclusions: The study shows that an increase in [Cl–]i may be involved in the Ca2+ influx in response to bradykinin and thapsigargin and that MLCK might be involved in the Cl– response. We suggest that MLCK might be involved in the Cl–-sensitive endothelial Ca2+ responses to bradykinin and thapsigargin.
KEYWORDS Endothelial factors; Calcium (cellular)
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