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Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.

Authors: Thomas, DW  Mannon, RB  Mannon, PJ  Latour, A  Oliver, JA  Hoffman, M  Smithies, O  Koller, BH  Coffman, TM 
Citation: Thomas DW, etal., J Clin Invest. 1998 Dec 1;102(11):1994-2001.
Pubmed: (View Article at PubMed) PMID:9835625
DOI: Full-text: DOI:10.1172/JCI5116

Thromboxane A2 (TXA2) is a labile metabolite of arachidonic acid that has potent biological effects. Its actions are mediated by G protein-coupled thromboxane-prostanoid (TP) receptors. TP receptors have been implicated in the pathogenesis of cardiovascular diseases. To investigate the physiological functions of TP receptors, we generated TP receptor-deficient mice by gene targeting. Tp-/- animals reproduce and survive in expected numbers, and their major organ systems are normal. Thromboxane agonist binding cannot be detected in tissues from Tp-/- mice. Bleeding times are prolonged in Tp-/- mice and their platelets do not aggregate after exposure to TXA2 agonists. Aggregation responses after collagen stimulation are also delayed, although ADP-stimulated aggregation is normal. Infusion of the TP receptor agonist U-46619 causes transient increases in blood pressure followed by cardiovascular collapse in wild-type mice, but U-46619 caused no hemodynamic effect in Tp-/- mice. Tp-/- mice are also resistant to arachidonic acid-induced shock, although arachidonic acid signifi-cantly reduced blood pressure in Tp-/- mice. In summary, Tp-/- mice have a mild bleeding disorder and altered vascular responses to TXA2 and arachidonic acid. Our studies suggest that most of the recognized functions of TXA2 are mediated by the single known Tp gene locus.

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CRRD Object Information
CRRD ID: 11059528
Created: 2016-04-15
Species: All species
Last Modified: 2016-04-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.