Effects of antidepressants on G protein-coupled receptor signaling and viability in Xenopus laevis oocytes
| Autor: | Klaus Hahnenkamp, Barbara Tröster, Cristina E. Vitan, Markus W. Hollmann, Christel G. den Bakker, Danja Strümper, Marcel E. Durieux |
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| Přispěvatelé: | Anesthesiology |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Cell Survival
G protein Xenopus Receptors Cell Surface Antidepressive Agents Tricyclic Pharmacology Xenopus laevis chemistry.chemical_compound GTP-Binding Proteins Lysophosphatidic acid medicine Animals G protein-coupled receptor Dose-Response Relationship Drug biology business.industry biology.organism_classification G Protein-Coupled Receptor Signaling Anesthesiology and Pain Medicine chemistry Mechanism of action Oocytes Female Serotonin medicine.symptom Signal transduction business |
| Zdroj: | Anesthesiology, 99(4), 911-917. Lippincott Williams and Wilkins |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/00000542-200310000-00025 |
| Popis: | Background Tricyclic antidepressants are structurally related to local anesthetics, suggesting that part of their analgesic action may result from properties shared with local anesthetics. Because local anesthetics block G protein-coupled receptor signaling (which explains, in part, their inflammatory modulating properties), the authors studied whether antidepressants have similar effects. Methods Peak Ca-activated Cl currents induced in Xenopus laevis oocytes by lysophosphatidic acid (10(-4) m) were measured using a voltage clamp. The effects of a 30-, 120-, or 240-min incubation in amitriptyline, nortriptyline, imipramine, or fluoxetine were determined. Results After a 30-min incubation, low concentrations (10(-7)-10(-5) m) of antidepressants had no effect on lysophosphatidic acid-induced currents. After prolonged incubation, only amitriptyline or nortriptyline inhibited lysophosphatidic acid signaling (each to 58% of the control response at 10(-7) m after 240 min). At low concentrations, none of the compounds induced membrane damage (defined as a holding current of > 1 microA, 2% in control cells). Imipramine at 10(-3) m induced damage in 100% of oocytes, and fluoxetine at 10(-4) m induced damage in 71% of oocytes (P < 0.05 vs. control). Amitriptyline and nortriptyline had no effect. Conclusions These findings are in part different from those obtained with local anesthetics and suggest that interference with G protein-coupled signaling might explain, in part, the analgesic properties of some antidepressants. However, use of antidepressants in high concentrations may be associated with cellular toxicity. |
| Databáze: | OpenAIRE |
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