| Effect of a stimulant of guanylate cyclase, sin 1, on calcium movements and phospholipase C activation in thrombin-stimulated human platelets. | |
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MedLine Citation:
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PMID: 2833275 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effects of sin 1, a metabolite of an antianginal agent, molsidomine, were investigated on human platelet activation induced by thrombin. This drug promoted a slight inhibition of serotonin release in a medium containing 1 mM Ca2+ or 1 mM EGTA (from 63% to 46% and from 57% to 41% of total serotonin secretion, respectively, with the highest dose used). Under these conditions, Ca2+ movements, monitored by quin 2 fluorescence, were markedly impaired. The most pronounced effect was towards Ca2+ influx, which presented a rapid inhibition with low doses. In the presence of external calcium, thrombin raised cytoplasmic free Ca2+ concentration from 100 nM to 1277 nM. This was reduced to 466 nM and 175 nM with 10(-7) M and 10(-4) M sin 1, respectively. Ca2+ mobilization from internal stores was less inhibited, since cytoplasmic free Ca2+ movements, sin 1 was tested on [32P] phosphatidic acid synthesis resulting from phospholipase C activation induced by thrombin. Phosphatidic acid labelling displayed a maximal inhibition of 43-50% with the highest doses of sin 1 (10(-4) M-10(-3) M) with or without Ca2+ in the incubation medium. However, this effect appeared much more sensitive to sin 1 in the presence of external Ca2+ (25% at 10(-7) M sin 1 with external Ca2+ against 12% at the same sin 1 concentration with EGTA). This discrepancy might be explained by the difference of cGMP level obtained when platelets were treated by sin 1 in the presence or in the absence of Ca2+ in the medium. This study shows that the major target of sin 1 via cGMP is not platelet phospholipase C as previously described, but inhibition of Ca2+ influx through plasma membrane. |
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Authors:
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M F Simon; H Chap; L Douste-Blazy |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical pharmacology Volume: 37 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1988 Apr |
Date Detail:
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Created Date: 1988-05-10 Completed Date: 1988-05-10 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1263-9 Citation Subset: IM |
Affiliation:
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INSERM Unité 101, Biochimie des Lipides, Hôpital Purpan, Toulouse, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blood Platelets
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drug effects*,
metabolism Calcium / metabolism* Cyclic GMP / metabolism Dose-Response Relationship, Drug Enzyme Activation / drug effects Humans Molsidomine / analogs & derivatives*, pharmacology Phosphatidic Acids / metabolism Serotonin / secretion Thrombin / pharmacology* Type C Phospholipases / analysis* |
| Chemical | |
Reg. No./Substance:
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0/Phosphatidic Acids; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 50-67-9/Serotonin; 7440-70-2/Calcium; 7665-99-8/Cyclic GMP; EC 3.1.4.-/Type C Phospholipases; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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