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(Circulation Research. 2006;98:582.)
© 2006 American Heart Association, Inc.

Editorials

Is cAMP Good or Bad?

Depends on Where It’s Made

Rodolphe Fischmeister

From INSERM U769, Châtenay-Malabry, F-92296 France, and Université Paris-Sud, Faculté de Pharmacie, IFR141, Châtenay-Malabry, F-92286 France.

Correspondence to Rodolphe FISCHMEISTER, INSERM U769, Faculté de Pharmacie, 5, Rue J.-B. Clément, F-92296 Châtenay-Malabry Cedex, France. E-mail fisch@vjf.inserm.fr

See related article, pages 675–681

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Endothelium of the vascular system forms a semipermeable barrier between blood and the interstitial space that serves to control and restrict the luminal to abluminal movement of water, plasma proteins, and other solutes.¹ During inflammation, mediators such as thrombin, histamine, and platelet activating factor (PAF) induce vascular leakage defined as an increased endothelial permeability to plasma proteins. In the lung, disruption of the barrier formed by pulmonary microvascular endothelial cells (PMVECs) occurs during inflammatory disease states such as acute lung injury and acute respiratory distress syndrome. Endothelial permeability to macromolecules occurs via the formation of small gaps between (paracellular) or through (transcellular) cells and is controlled by cell shape and cell adhesion through a balance of opposite mechanical forces; contractile forces generated by actomyosin motor function, tethering forces generated by adhesive proteins at the cell–cell border, and focal adhesions at the cell–matrix border.² Because of its central role in mechanical processes, Ca²⁺ is an important regulator of endothelial permeability. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) is increased in PMVECs on binding of proinflammatory mediators to their respective membrane receptors, and subsequent activation of the G_q protein–mediated signaling cascade. In particular, this rise in [Ca²⁺]_i is essential for the generation of endothelial cell paracellular gaps. Other downstream major actors in this Ca²⁺-sensitizing cascade include PKC, Ca²⁺-dependent myosin light chain kinase (MLCK), and the monomeric GTPase RhoA.

Whereas elevated [Ca²⁺]_i increases endothelial barrier permeability, increased cAMP has the opposite effect.³ Changes in this ubiquitous second messenger are governed . . . [Full Text of this Article]

Related Article:

Soluble Adenylyl Cyclase Reveals the Significance of cAMP Compartmentation on Pulmonary Microvascular Endothelial Cell Barrier

Sarah L. Sayner, Mikhail Alexeyev, Carmen W. Dessauer, and Troy Stevens
Circ. Res. 2006 98: 675-681. [Abstract] [Full Text] [PDF]

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