| http://purl.uniprot.org/citations/9855623 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/9855623 | http://www.w3.org/2000/01/rdf-schema#comment | "Nitric oxide (NO), the physiological activator of soluble guanylyl cyclase (sGC), induces inhibitory effects on platelet activation via elevation of cGMP levels and stimulation of the cGMP-dependent protein kinase. YC-1, a benzylindazole derivative, was shown to activate sGC in intact platelets, resulting in inhibition of platelet aggregation. In a previous study, we demonstrated that YC-1 not only stimulates purified sGC but also potentiates the stimulatory action of submaximally effective NO and carbon monoxide (CO) concentrations. Here, we investigated the potentiating effect of YC-1 in intact platelets. YC-1 together with NO or CO led to complete inhibition of platelet aggregation at concentrations that were ineffective by themselves. Maximally effective 2, 2-diethyl-1-nitroso-oxyhydrazine (3 microM) and YC-1 (100 microM) concentrations each elevated the cGMP levels in intact platelets approximately 13-fold, and administration of the two drugs together resulted in enormous potentiation of cGMP formation, which greatly exceeded the effect on the purified enzyme and yielded a >1300-fold increase in cGMP levels. Similar results were obtained using CO instead of NO. Furthermore, YC-1 not only stimulated sGC but also inhibited cGMP-hydrolyzing phosphodiesterases in platelets. The enormous elevation of cGMP levels led to enhanced phosphorylation of the cGMP-dependent protein kinase substrate vasodilator-stimulated phosphoprotein. Thus, by the combination of two effects (i.e., potentiation of NO-induced sGC stimulation and phosphodiesterase inhibition), YC-1-like substances are potent activators of the sGC/cGMP pathways and are therefore interesting candidates to act as modulators of cGMP-mediated effects, especially within the cardiovascular system."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.54.6.962"xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/author | "Walter U."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/author | "Friebe A."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/author | "Koesling D."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/author | "Schultz G."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/author | "Smolenski A."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/author | "Mullershausen F."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/date | "1998"xsd:gYear |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/name | "Mol Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/pages | "962-967"xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/title | "YC-1 potentiates nitric oxide- and carbon monoxide-induced cyclic GMP effects in human platelets."xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://purl.uniprot.org/core/volume | "54"xsd:string |
| http://purl.uniprot.org/citations/9855623 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/9855623 |
| http://purl.uniprot.org/citations/9855623 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/9855623 |
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| http://purl.uniprot.org/uniprot/#_Q02153-mappedCitation-9855623 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/9855623 |
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| http://purl.uniprot.org/uniprot/#_P33402-mappedCitation-9855623 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/9855623 |
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| http://purl.uniprot.org/uniprot/P33402 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/9855623 |
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| http://purl.uniprot.org/uniprot/O75343 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/9855623 |