Nongenomic Signaling of the Retinoid X Receptor Through Binding and Inhibiting Gq in Human Platelets

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2007 Jan 11

PMID 17213293

Citations 35

Authors

Leonardo A Moraes

Karen E Swales

Jessica A Wray

Amilcar Damazo

Jonathan M Gibbins

Timothy D Warner

David Bishop-Bailey

Affiliations

Soon will be listed here.

Abstract

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.

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