التفاصيل البيبلوغرافية
| العنوان: |
Serotonin 5-HT2B receptor loss of function mutation in a patient with fenfluramine-associated primary pulmonary hypertension |
| المؤلفون: |
Blanpain, Cédric, Le Poul, Emmanuel, Parma, Jasmine, Knoop, Christiane, Detheux, Michel, Parmentier, Marc, Vassart, Gilbert, Abramowicz, Marc J. |
| المصدر: |
Cardiovascular Research; Dec2003, Vol. 60 Issue 3, p518, 11p |
| مصطلحات موضوعية: |
SEROTONIN, APPETITE depressants, FENFLURAMINE, PULMONARY hypertension |
| مستخلص: |
Objective: Appetite-suppressant drug fenfluramine is implicated in primary pulmonary hypertension (PPH) but the molecular pathways that mediate this effect are unknown. A mouse model incriminates the serotonin 5-HT2B receptor but contrasts with other models where this receptor has been shown to mediate pulmonary arterial relaxation via nitric oxide production. Methods: We analyzed the human 5-HT2B gene in 10 patients with appetite-suppressant drug-associated PPH. Results: A mutation causing premature truncation of the protein product was found in one patient. The mutation was not found in 80 control subjects and no 5-HT2B mutation was found in 18 PPH patients not associated with appetite-suppressants. Functional analysis of the transfected receptor expressed either transiently in COS cells or stably in CHO cells demonstrated that the mutated receptor fails to activate the second messenger inositol-phosphates cascade and subsequent intracellular calcium release, in spite of normal expression at the cell membrane. The mutated receptor had no constitutive activity, and produced no dominant negative effect on the wild-type receptor. Conclusion: Loss of serotonin 5-HT2B receptor function may predispose to fenfluramine-associated PPH in man. [Copyright &y& Elsevier] |
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| قاعدة البيانات: |
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