PMID- 17213293
OWN - NLM
STAT- MEDLINE
DCOM- 20070605
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 109
IP  - 9
DP  - 2007 May 1
TI  - Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq 
      in human platelets.
PG  - 3741-4
AB  - 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.
FAU - Moraes, Leonardo A
AU  - Moraes LA
AD  - Cardiac, Vascular and Inflammation Research, William Harvey Research Institute, 
      Barts and the London, Queen Mary University of London, Charterhouse Square, 
      London, UK.
FAU - Swales, Karen E
AU  - Swales KE
FAU - Wray, Jessica A
AU  - Wray JA
FAU - Damazo, Amilcar
AU  - Damazo A
FAU - Gibbins, Jonathan M
AU  - Gibbins JM
FAU - Warner, Timothy D
AU  - Warner TD
FAU - Bishop-Bailey, David
AU  - Bishop-Bailey D
LA  - eng
GR  - 074361/Z/04/Z/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070109
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Ligands)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 0 (Retinoid X Receptor beta)
RN  - 57576-52-0 (Thromboxane A2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
SB  - IM
MH  - Blood Platelets/cytology/*metabolism
MH  - Calcium Signaling/drug effects/*physiology
MH  - Cell Line
MH  - GTP-Binding Protein alpha Subunits, Gq-G11/*metabolism
MH  - Humans
MH  - Ligands
MH  - Platelet Aggregation/drug effects/*physiology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Retinoid X Receptor alpha/*metabolism
MH  - Retinoid X Receptor beta/*metabolism
MH  - Thromboxane A2/metabolism
PMC - PMC2612640
EDAT- 2007/01/11 09:00
MHDA- 2007/06/06 09:00
PMCR- 2007/05/01
CRDT- 2007/01/11 09:00
PHST- 2007/01/11 09:00 [pubmed]
PHST- 2007/06/06 09:00 [medline]
PHST- 2007/01/11 09:00 [entrez]
PHST- 2007/05/01 00:00 [pmc-release]
AID - S0006-4971(20)41619-2 [pii]
AID - 2006/022566 [pii]
AID - 10.1182/blood-2006-05-022566 [doi]
PST - ppublish
SO  - Blood. 2007 May 1;109(9):3741-4. doi: 10.1182/blood-2006-05-022566. Epub 2007 Jan 
      9.