Adenosine regulates tissue factor expression on endothelial cells.

Abstract

The aim of this study was to evaluate the inhibitory activity of adenosine on tumor necrosis factor-alpha (TNF), thrombin-, or phorbol 12-myristate 13-acetate (PMA)-induced tissue factor (TF) expression on human umbilical vein endothelial cells (HUVECs). This inhibitory effect of adenosine was found to be counteracted by the non-selective adenosine receptor (AR) antagonist, 8-(p-sulfophenyl) theophylline. To clarify the role of ARs (A1, A2a, A2b, and A3) in this regulation, we evaluated the effect of several agonists and antagonists specific for AR-subclass on TF expression. The selective A2aAR agonist, 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride (CGS 21680), the A3AR agonist, N6-2-(4-aminophenyl) ethyladenosine (APNEA), and the A1AR antagonist, 1,3-dipropyl-8-(2-amino-4-chlorophenyl) xanthine (PACPX) each inhibited TF activity expression induced by TNF, thrombin, or PMA on HUVECs. In contrast, the selective A1AR agonist, chloro-N6-cyclopentyladenosine (CCPA) and the A2AR antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX) enhanced each stimulant-induced TF activity expression. All agonist or antagonist alone did not alter the basal TF expression on HUVECs. Our results suggest that stimulation of A2aAR and A3AR down-regulates and that of A1AR up-regulates the endothelial cell TF expression induced by TNF, PMA, or thrombin. Thus, it appears that adenosine itself may exert anticoagulant activity on vascular endothelial cells via its A2a and A3 receptors, particularly during ischemic or atherosclerotic processes which are known to be associated with local increased levels of adenosine.

• Authors: H Deguchi, H Takeya, H Urano, E C Gabazza, H Zhou, K Suzuki
• Journal: Thrombosis research (Thromb Res) Vol. 91 Issue 2 Pg. 57-64 (Jul 15 1998) ISSN: 0049-3848 [Print] United States
• PMID: 9722021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiovascular Agents
• Hemostatics
• Purinergic P1 Receptor Agonists
• Purinergic P1 Receptor Antagonists
• Tumor Necrosis Factor-alpha
• Xanthines
• Thromboplastin
• Thrombin
• 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine
• Adenosine
• Tetradecanoylphorbol Acetate

Topics

• Adenosine (chemistry, pharmacology, physiology)
• Cardiovascular Agents (chemistry, pharmacology)
• Cells, Cultured
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Hemostatics (pharmacology)
• Humans
• Infant, Newborn
• Purinergic P1 Receptor Agonists
• Purinergic P1 Receptor Antagonists
• Tetradecanoylphorbol Acetate (pharmacology)
• Thrombin (pharmacology)
• Thromboplastin (biosynthesis, drug effects)
• Tumor Necrosis Factor-alpha (pharmacology)
• Umbilical Veins (cytology, drug effects, metabolism)
• Xanthines (pharmacology)