Moraes Leonardo A, Swales Karen E, Wray Jessica A, Damazo Amilcar, Gibbins Jonathan M, Warner Timothy D, Bishop-Bailey David
Cardiac, Vascular and Inflammation Research, William Harvey Research Institute, Barts and the London, Queen Mary University of London, Charterhouse Square, London, UK.
Blood. 2007 May 1;109(9):3741-4. doi: 10.1182/blood-2006-05-022566. Epub 2007 Jan 9.
Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) gamma, PPARbeta, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXRalpha and RXRbeta. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families.
维甲酸X受体（RXRs）是重要的转录核激素受体，可作为同二聚体或至少四分之一已知人类核受体的结合伴侣发挥作用。核受体的功能性非基因组效应了解甚少；然而，最近过氧化物酶体增殖物激活受体（PPAR）γ、PPARβ和糖皮质激素受体在人类血小板中均被发现具有活性。人类血小板表达RXRα和RXRβ。RXR配体抑制血小板聚集以及向ADP和血栓素A2（TXA2）受体释放TXA2，但对胶原蛋白的抑制作用较弱。ADP和TXA2均通过G蛋白Gq发出信号。RXR以配体依赖的方式快速结合Gq，而不结合Gi/z/o/t/gust，并抑制Gq诱导的Rac激活和细胞内钙释放。我们提出，RXR配体可能通过抑制血小板激活而具有有益的临床作用。此外，我们的结果证明了核受体作用的一种新型非基因组模式以及G蛋白和核受体信号家族之间的功能性相互作用。
