Schinner, Elisabeth and Salb, Katharina and Schlossmann, Jens (2011) Signaling via IRAG is essential for NO/cGMP-dependent inhibition of platelet activation. PLATELETS, 22 (3). pp. 217-227. ISSN 0953-7104, 1369-1635
Full text not available from this repository. (Request a copy)Abstract
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.</.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE-C; NITRIC-OXIDE; THROMBUS FORMATION; INTRACELLULAR CA2+; GRANULE SECRETION; CALDAG-GEFI; AGGREGATION; RECEPTOR; CGMP; ADHESION; Nitric oxide/NO; signal transduction; IRAG; platelet adhesion; granule secretion |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jul 2020 06:24 |
| Last Modified: | 02 Jul 2020 06:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21667 |
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