HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/L1048    most recent 90259.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Sacks, R. S. Articles by Yuan, J. X.-J. Search for Related Content PubMed PubMed Citation Articles by Sacks, R. S. Articles by Yuan, J. X.-J.

Thrombin-mediated increases in cytosolic [Ca²⁺] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Diego, La Jolla, California

Submitted 2 April 2008 ; accepted in final form 23 September 2008

Thrombin is a procoagulant inflammatory agonist that can disrupt the endothelium-lumen barrier in the lung by causing contraction of endothelial cells and promote pulmonary cell proliferation. Both contraction and proliferation require increases in cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt). In this study, we compared the effect of thrombin on Ca²⁺ signaling in human pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells. Thrombin increased the [Ca²⁺]_cyt in both cell types; however, the transient response was significantly higher and recovered quicker in the PASMC, suggesting different mechanisms may contribute to thrombin-mediated increases in [Ca²⁺]_cyt in these cell types. Depletion of intracellular stores with cyclopiazonic acid (CPA) in the absence of extracellular Ca²⁺ induced calcium transients representative of those observed in response to thrombin in both cell types. Interestingly, CPA pretreatment significantly attenuated thrombin-induced Ca²⁺ release in PASMC; this attenuation was not apparent in PAEC, indicating that a PAEC-specific mechanism was targeted by thrombin. Treatment with a combination of CPA, caffeine, and ryanodine also failed to abolish the thrombin-induced Ca²⁺ transient in PAEC. Notably, thrombin-induced receptor-mediated calcium influx was still observed in PASMC after CPA pretreatment in the presence of extracellular Ca²⁺. Ca²⁺ oscillations were triggered by thrombin in PASMC resulting from a balance of extracellular Ca²⁺ influx and Ca²⁺ reuptake by the sarcoplasmic reticulum. The data show that thrombin induces increases in intracellular calcium in PASMC and PAEC with a distinct CPA-, caffeine-, and ryanodine-insensitive release existing only in PAEC. Furthermore, a dynamic balance between Ca²⁺ influx, intracellular Ca²⁺ release, and reuptake underlie the Ca²⁺ transients evoked by thrombin in some PASMC. Understanding of such mechanisms will provide an important insight into thrombin-mediated vascular injury during hypertension.

sarcoplasmic and endoplasmic reticulum; Ca²⁺ store

This article has been cited by other articles:

				A. L. Firth, J. Yau, A. White, P. G. Chiles, J. J. Marsh, T. A. Morris, and J. X.-J. Yuan Chronic exposure to fibrin and fibrinogen differentially regulates intracellular Ca2+ in human pulmonary arterial smooth muscle and endothelial cells Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L979 - L986. [Abstract] [Full Text] [PDF]