Human genetic variations in the 5HT2A receptor
| Autor: | Tom A. Pfeifer, Peter J. K. Knight, Layne Harvey, Caixia Ma, Ronald E. Reid, Thomas A. Grigliatti |
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| Rok vydání: | 2003 |
| Předmět: |
Agonist
Serotonin medicine.medical_specialty medicine.drug_class 5-HT2A receptor Blotting Western Loxapine Spodoptera Biology Pharmacology Binding Competitive Polymerase Chain Reaction Polymorphism Single Nucleotide Cell Line Transformation Genetic Internal medicine Genetics medicine Animals Humans Receptor Serotonin 5-HT2A General Pharmacology Toxicology and Pharmaceutics Receptor Clozapine DNA Primers Genetic Variation Free Radical Scavengers Endocrinology Receptors Serotonin Serotonin Antagonists Signal transduction Endogenous agonist Antipsychotic Agents Plasmids medicine.drug |
| Zdroj: | Pharmacogenetics. 13:107-118 |
| ISSN: | 0960-314X |
| DOI: | 10.1097/00008571-200302000-00007 |
| Popis: | Objective to determine if the agonist serotonin and antagonists loxapine and clozapine have an altered potency for four allelic variants (T25N, I197V, A447V, and H452Y) of the human 5HT2A receptor when compared to the wild-type allele. Methods The receptor or its variants are studied in an in-vitro functional assay system consisting of a Sf9 insect cell line that is stably transformed with the human wild-type and mutant alleles. This assay system measures release of calcium stores due to receptor activation by agonists and inhibition of this agonist stimulated response by antagonists. Results Both loxapine and clozapine exhibit non-competitive antagonism of serotonin stimulation of the human 5HT2A receptor signal transduction system and loxapine is the more potent inhibitor. This study shows that the I197V allele requires a two-fold higher concentration of the atypical neuroleptic clozapine to inhibit serotonin stimulation compared to the wild-type receptor (P = 0.036). The I197V mutation does not affect the inhibition of serotonin stimulation by the typical neuroleptic loxapine nor does it alter the activation of the receptor by serotonin. It is also significant that the results of this study indicate that the T25N, A447V, and H452Y mutations in the human 5HT2A receptor do not significantly alter the response of the receptor to the agonist serotonin or the antagonists loxapine and clozapine. |
| Databáze: | OpenAIRE |
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