Use of recombinant human α2-adrenoceptors to characterize subtype selectivity of antagonist binding
| Autor: | Mika Scheinin, Kirsti Luomala, Sari Ala-Uotila, Anne Marjamäki |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Rauwolscine Oxymetazoline Biology Ligands Partial agonist Mice chemistry.chemical_compound Phentolamine Receptors Adrenergic alpha-2 Internal medicine Tumor Cells Cultured medicine Prazosin Animals Humans Receptor Adrenergic alpha-Antagonists Pharmacology Molecular biology Recombinant Proteins Yohimbine Endocrinology chemistry Heterologous expression medicine.drug |
| Zdroj: | European Journal of Pharmacology: Molecular Pharmacology. 246:219-226 |
| ISSN: | 0922-4106 |
| DOI: | 10.1016/0922-4106(93)90034-7 |
| Popis: | Cloning of the genes encoding three subtypes of human α 2 -adrenoceptors allows the separate heterologous expression of each subtype. We have generated stably transfected Shionogi S115 mouse mammary tumour cell lines expressing the human α 2 -adrenoceptor subtypes α 2 -C10, α 2 -C 2 , and α 2 -C4 at densities of 0.2–7 pmol/mg total cellular protein. Binding of [ 3 H]rauwolscine was inhibited by co-incubation of S115 cell homogenates with ten α 2 -adrenoceptor antagonists and oxymetazoline, a partial agonist known to discriminate the receptor subtypes. Other useful agents for discrimination of subtypes were prazosin, chlorpromazine, phentolamine, and yohimbine. The most sensitive indices for differences between the three subtypes were the binding inhibition coefficient (K i ) ratios chlorpromazie/oxymetazoline ( α 2 -C10 202; α 2 -C 0.004; α 2 -C4: 0.8), prazosin/oxymetazoline (430; 0.03; 0.5) and chlorpromazine/atipamezole (1612; 5.8; 77). Correlation analysis between our results for human-type receptors and published data for their rat α 2 -adrenoceptor homologues demonstrated excellent general agreement, with some interspecies differences in the affinity of rauwolscine, phentolamine and oxymetazoline. The use of recombinant human receptors produced in stably transfected cell lines should facilitate the development of new, subtype-selective α 2 -adrenoceptor ligands. |
| Databáze: | OpenAIRE |
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