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The Human Serotonin 1A Receptor Expressed in Neuronal Cells: Toward a Native Environment for Neuronal Receptors

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1. The serotonin1A (5-HT1A) receptor is an important representative of G-protein coupled family of receptors. It is the most extensively studied among the serotonin receptors, and appears to be involved in various behavioral and cognitive functions.

2. We report here the pharmacological and functional characterization of the human serotonin1A receptor stably expressed in HN2 cell line, which is a hybrid cell line between hippocampal cells and mouse neuroblastoma.

3. Our results show that serotonin1A receptors in HN2-5-HT1AR cells display ligand-binding properties that closely mimic binding properties observed with native receptors. We further demonstrate that the differential discrimination of G-protein coupling by the specific agonist and antagonist, a hallmark of the native receptor, is maintained for the receptor in HN2-5-HT1AR cells. Importantly, the serotonin1A receptor in HN2-5-HT1AR cells shows efficient downstream signalling by reducing cellular cyclic AMP levels.

4. We conclude that serotonin1A receptors expressed in HN2-5-HT1AR cells represent a useful model system to study serotonin1A receptor biology, and is a potential system for solubilization and purification of the receptor in native-like membrane environment.

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ACKNOWLEDGMENTS

This work was supported by the Council of Scientific and Industrial Research, Government of India. Y. D. P. thanks the Council of Scientific and Industrial Research for the award of a Senior Research Fellowship. A. C. is an Honorary Faculty Member of the Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India. We gratefully acknowledge Dr. Probal Banerjee for the kind gift of HN2-5 cells and for sharing useful information, and Dr. K. G. Harikumar for preliminary experiments. We thank members of our laboratory for critically reading the manuscript.

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Paila, Y.D., Chattopadhyay, A. The Human Serotonin 1A Receptor Expressed in Neuronal Cells: Toward a Native Environment for Neuronal Receptors. Cell Mol Neurobiol 26, 923–940 (2006). https://doi.org/10.1007/PL00021779

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