Progress in neuro-psychopharmacology & biological psychiatry, Jan 10, 2012
The clinical efficacy of aripiprazole in the treatment of psychosis relies on a partial agonism a... more The clinical efficacy of aripiprazole in the treatment of psychosis relies on a partial agonism at D2 receptors. As the expression of this receptor differs physiologically between pre- and post-synaptic sites and is affected by pathological conditions or pharmacological treatments, it appears difficult to predict the clinical response to partial agonists. In addition, the response to this novel antipsychotic was shown to depend on the cell-line and the pathway analyzed, suggesting a functional selective profile at the D2 receptor. This study aims at examining the influence of receptor density and ionic environment on the pharmacological properties of aripiprazole. A cell line was developed in which the expression of the recombinant D2 receptor can be tightly manipulated using doxycycline and sodium butyrate. The potency and efficacy of aripiprazole and other reference D2 receptor ligands were examined in [35S]GTPγS binding assays, in buffers containing either NaCl or N-methyl-D-gluc...
Methods in molecular biology (Clifton, N.J.), 2011
Biochemical or pharmacological studies of G protein-coupled receptors (GPCRs) are widely conducte... more Biochemical or pharmacological studies of G protein-coupled receptors (GPCRs) are widely conducted in transfected mammalian cells. A variety of commercially available systems allow the generation of stable cell-lines in which expression of the recombinant receptor can be induced on addition of a defined chemical to the culture medium, which operates as a control switch for the transcription of the cloned sequence. Such systems offer the possibility to induce graded levels of receptor expression in the experimental model, or to induce an abrupt downregulation of receptor expression during the maintenance of the cell-line. This chapter provides an overview of the different systems available and provides methods for the generation and validation of stably transfected cell-lines expressing the GPCR of choice.
Progress in neuro-psychopharmacology & biological psychiatry, Jan 10, 2012
The clinical efficacy of aripiprazole in the treatment of psychosis relies on a partial agonism a... more The clinical efficacy of aripiprazole in the treatment of psychosis relies on a partial agonism at D2 receptors. As the expression of this receptor differs physiologically between pre- and post-synaptic sites and is affected by pathological conditions or pharmacological treatments, it appears difficult to predict the clinical response to partial agonists. In addition, the response to this novel antipsychotic was shown to depend on the cell-line and the pathway analyzed, suggesting a functional selective profile at the D2 receptor. This study aims at examining the influence of receptor density and ionic environment on the pharmacological properties of aripiprazole. A cell line was developed in which the expression of the recombinant D2 receptor can be tightly manipulated using doxycycline and sodium butyrate. The potency and efficacy of aripiprazole and other reference D2 receptor ligands were examined in [35S]GTPγS binding assays, in buffers containing either NaCl or N-methyl-D-gluc...
Methods in molecular biology (Clifton, N.J.), 2011
Biochemical or pharmacological studies of G protein-coupled receptors (GPCRs) are widely conducte... more Biochemical or pharmacological studies of G protein-coupled receptors (GPCRs) are widely conducted in transfected mammalian cells. A variety of commercially available systems allow the generation of stable cell-lines in which expression of the recombinant receptor can be induced on addition of a defined chemical to the culture medium, which operates as a control switch for the transcription of the cloned sequence. Such systems offer the possibility to induce graded levels of receptor expression in the experimental model, or to induce an abrupt downregulation of receptor expression during the maintenance of the cell-line. This chapter provides an overview of the different systems available and provides methods for the generation and validation of stably transfected cell-lines expressing the GPCR of choice.
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Papers by Beryl Koener