PMID- 21244222
OWN - NLM
STAT- MEDLINE
DCOM- 20110927
LR  - 20210118
IS  - 1369-1635 (Electronic)
IS  - 0953-7104 (Linking)
VI  - 22
IP  - 3
DP  - 2011
TI  - Signaling via IRAG is essential for NO/cGMP-dependent inhibition of platelet 
      activation.
PG  - 217-27
LID - 10.3109/09537104.2010.544151 [doi]
AB  - Platelet activation is strongly affected by nitric oxide/cyclic GMP (NO/cGMP) 
      signaling involving cGMP-dependent protein kinase I (cGKI). Previously it was 
      shown that interaction of the cGKI substrate IRAG with InsP(3)RI is essential for 
      NO/cguanosine monophosphate (GMP)-dependent inhibition of platelet aggregation in 
      vitro and in vivo. However, the role of Inositol-trisphosphate receptor 
      associated cGMP kinase substrate (IRAG) for platelet adhesion or granule 
      secretion was unknown. Here, we analysed the functional role of IRAG for platelet 
      activation. Murine IRAG-deficient platelets displayed enhanced aggregability 
      towards several agonists (collagen, thrombin and TxA2). NO- or cGMP-dependent 
      inhibition of agonist induced ATP- or 5-HT secretion from dense granules, and 
      P-selectin secretion from alpha granules was severely affected in IRAG-deficient 
      platelets. Concomitantly, the effect of NO/cGMP on platelet aggregation was 
      strongly reduced in IRAG-deficient platelets. Furthermore, GPIIb/IIIa-mediated 
      adhesion of platelets to fibrinogen could only weakly be inhibited in 
      IRAG-deficient mice contrary to wild-type (WT) mice. Our results suggest that 
      signaling via IRAG is essential for NO/cGMP-dependent inhibition of platelet 
      activation regarding granule secretion, aggregation and adhesion. This platelet 
      disorder might cause that the bleeding time of IRAG-deficient mice was reduced.
FAU - Schinner, Elisabeth
AU  - Schinner E
AD  - Pharmacology and Toxicology, University Regensburg, Universitatsstr. 31, 93040 
      Regensburg, Germany.
FAU - Salb, Katharina
AU  - Salb K
FAU - Schlossmann, Jens
AU  - Schlossmann J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110118
PL  - England
TA  - Platelets
JT  - Platelets
JID - 9208117
RN  - 0 (Enzyme Activators)
RN  - 0 (IRAG1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mrvi1 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Blood Platelets/enzymology/*metabolism
MH  - Cyclic GMP/*blood
MH  - Cyclic GMP-Dependent Protein Kinases/blood
MH  - Enzyme Activators/pharmacology
MH  - Humans
MH  - Membrane Proteins/*blood
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide/*blood
MH  - Phosphoproteins/*blood/deficiency/genetics
MH  - Platelet Activation/*physiology
MH  - Signal Transduction
EDAT- 2011/01/20 06:00
MHDA- 2011/09/29 06:00
CRDT- 2011/01/20 06:00
PHST- 2011/01/20 06:00 [entrez]
PHST- 2011/01/20 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
AID - 10.3109/09537104.2010.544151 [doi]
PST - ppublish
SO  - Platelets. 2011;22(3):217-27. doi: 10.3109/09537104.2010.544151. Epub 2011 Jan 
      18.