| Autor: | Sibylle Kiel, Manfred Göthert, Michael Brüss, Heinz Bönisch |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Intrinsic activity Biology Beta-1 adrenergic receptor Endocrinology Internal medicine Interleukin-21 receptor Genetics medicine 5-HT5A receptor General Pharmacology Toxicology and Pharmaceutics Signal transduction Receptor Glucagon-like peptide 1 receptor Protease-activated receptor 2 |
| Zdroj: | Pharmacogenetics. 13:119-126 |
| ISSN: | 0960-314X |
| DOI: | 10.1097/00008571-200302000-00008 |
| Popis: | The aim of this study, performed in stably transfected HEK293 cells, was to investigate whether expression of the naturally occurring Pro 279 Leu variant of the h5.HT 7(a) receptor (located in the third intracellular loop) is associated with changes in the pharmacological properties and/or second messenger formation compared to the wild-type receptor. Radioligand binding of[ 3 H]5-carboxamidotryptamine ([ 3 H]5-CT) to membranes and stimulation of[ 3 H]cAMP formation in whole cells evoked by 5-HT receptor agonists were determined. Maximum binding (B max ) to, and affinity (K D ) of [ 3 H]5-CT for, the variant receptor and the wild-type receptor were equal. All agonists and antagonists investigated exhibited no differences in affinity between the variant receptor and the wild-type receptor. However, the intrinsic activity of the 5-HT receptor agonists 5-HT, 5-CT, RU24969 and 8-OH-DPAT in stimulating [ 3 H]cAMP accumulation in the cells expressing the Pro 279 Leu variant was almost abolished and their potency was 2.9-4.3-fold lower. Despite its affinity for both receptor isoforms, sumatriptan did not stimulate the accumulation of cAMP. In individuals expressing the Pro 279 Leu variant of the h5-HT 7(a) receptor, a considerable attenuation of its function may be predicted. This may have relevance for the action of new classes of drugs which affect circadian rhythm or psychiatric diseases, such as schizophrenia. |
| Databáze: | OpenAIRE |
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