Received for publication January 20, 2006.
Revised June 12, 2006.
Accepted for publication June 13, 2006.

Regional differences in the coupling of 5-HT_1A receptors to G proteins in the rat brain

Abstract

Numerous data showed that 5-HT_1A receptors couple to Go/i proteins for signal transduction. However, the subunit isoforms really involved in 5-HT_1A receptor coupling in brain remain to be identified. Moreover, regional differences in the functional characteristics of brain 5-HT_1A receptors have been repeatedly evidenced. Because such differences could be due to variations in G proteins interacting with the same receptor, relevant approaches were used for identifying subunits physically coupled to 5-HT_1A receptors in different regions of the rat brain. Using immunoaffinity chromatography coupled to western blot detection, 5-HT_1A receptors were found to interact equally with Go and Gi3 in the cerebral cortex, mainly with Go and weakly with Gi3 in the hippocampus and exclusively with Gi3 in the anterior raphe area. In the hypothalamus, 5-HT_1A receptors appeared to be coupled to the latter two G proteins plus Gi1 and Gz. Complementary experiments based on an antibody capture technique coupled to both classical radioactivity and scintillation proximity assay detections showed that hippocampal 5-HT_1A receptor stimulation induced [³⁵S]GTP--S binding to immunoprecipitates with Gi3 and Go antisera. In the anterior raphe, such 55-HT_1A receptor-mediated effect was obtained with Gi3 antiserum only. These results demonstrated the existence of regional differences in the coupling of 5-HT_1A receptors to G-proteins in the rat brain. In the anterior raphe, 5-HT_1A receptors appear to interact specifically with Gi3 whereas, in the hippocampus, they are mainly coupled to Go proteins. Such a disparity in G-protein coupling might explain regional differences in adaptive regulations of brain 5-HT_1A receptors.

Key words: Serotonin, Gi family, G protein regulation, Desensitization/uncoupling

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