Abstract：
:Thromboxane A(2) (TXA(2)), an unstable arachidonic acid metabolite, elicits diverse physiological/pathophysiological actions, including platelet aggregation and smooth muscle contraction. TXA(2) has been shown to be involved in allergies, modulation of acquired immunity, atherogenesis, neovascularization, and metastasis of cancer cells. The TXA(2) receptor (TP) communicates mainly with G(q) and G(13), resulting in phospholipase C activation and RhoGEF activation, respectively. In addition, TP couples with G(11), G(12), G(13), G(14), G(15), G(16), G(i), G(s) and G(h). TP is widely distributed in the body, and is expressed at high levels in thymus and spleen. The second extracellular loop of TP is an important ligand-binding site, and Asp(193) is a key amino acid. There are two alternatively spliced isoforms of TP, TPalpha and TPbeta, which differ only in their C-terminals. TPalpha and TPbeta communicate with different G proteins, and undergo hetero-dimerization, resulting in changes in intracellular traffic and receptor protein conformations. TP cross-talks with receptor tyrosine kinases, such as EGF receptor, to induce cell proliferation and differentiation. TP is glycosylated in the N-terminal region for recruitment to plasma membranes. Furthermore, TP conformation is changed by coupling to G proteins, showing several states of agonist binding. Finally, several drugs modify TP-mediated events; these include cyclooxygenase inhibitors, TXA(2) synthase inhibitors and TP antagonists. Some flavonoids of natural origin also have TP receptor antagonistic activity. Recent advances in TP research have clarified TXA(2)-mediated events in detail, and further study will supply more beneficial information about TXA(2) pathophysiology.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Nakahata Ndoi
10.1016/j.pharmthera.2008.01.001subject
Has Abstractpub_date
2008-04-01 00:00:00pages
18-35issue
1eissn
0163-7258issn
1879-016Xpii
S0163-7258(08)00012-0journal_volume
118pub_type
杂志文章,评审abstract：:Nitric oxide (NO) exerts a variety of biological actions under both physiological and pathological conditions. NO is synthesized by three distinct NO synthase (NOS) isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS), all of which are expressed in the human cardiovascular system. The role...
journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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