Epinephrine correction of impaired platelet thromboxane receptor signaling
| Autor: | P. C. Dunlop, Gerhard J. Johnson, Linda A. Leis |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Blood Platelets
medicine.medical_specialty Nitrosamines Epinephrine Physiology Molecular Sequence Data Receptors Thromboxane Palmitates Inositol 1 4 5-Trisphosphate Sulfur Radioisotopes Tritium GTP Phosphohydrolases Iodine Radioisotopes Thromboxane receptor Thromboxane A2 chemistry.chemical_compound Dogs GTP-Binding Proteins Internal medicine medicine Animals Humans Vasoconstrictor Agents Platelet Amino Acid Sequence Carbon Radioisotopes Platelet activation Phosphorylation Chemistry Cell Biology Platelet Activation Kinetics Endocrinology Eicosanoid Guanosine 5'-O-(3-Thiotriphosphate) 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Catecholamine Signal transduction Mutagens Signal Transduction medicine.drug |
| Zdroj: | American Journal of Physiology-Cell Physiology. 279:C1760-C1771 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.2000.279.6.c1760 |
| Popis: | This study evaluated the mechanism of epinephrine potentiation of platelet secretion induced by thromboxane A2(TXA2). Dog platelets that do not secrete in response to TXA2alone (TXA2−) were compared with dog platelets that do secrete (TXA2+) and with human platelets. TXA2− platelets had impaired TXA2receptor (TP receptor)-G protein coupling, indicated by 1) impaired stimulated GTPase activity, 2) elevated basal guanosine 5′- O-(3-thiotriphosphate) binding, and 3) elevated Gαqpalmitate turnover that was corrected by preexposure to epinephrine. Kinetic agonist binding studies revealed biphasic dog and human platelet TP receptor association and dissociation. TXA2− and TP receptor-desensitized TXA2+ dog and human platelets had altered ligand binding parameters compared with untreated TXA2+ or human platelets. These parameters were reversed, along with impaired secretion, by epinephrine. Basal phosphorylation of TXA2− platelet TP receptors was elevated 60% and was normalized by epinephrine. Epinephrine potentiates platelet secretion stimulated by TXA2by reducing basal TP receptor phosphorylation and facilitating TP receptor-G protein coupling in TXA2− platelets and, probably, in normal platelets as well. |
| Databáze: | OpenAIRE |
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