Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents.
The anorexigenic effect of serotonergic compounds has largely been attributed to activation of serotonin 2C receptors (Htr2cs). Using mouse genetic models in which Htr2c can be selectively deleted or restored (in Htr2c-null mice), we investigate the role of Htr2c in forebrain Sim1 neurons. Unexpectedly, we find that Htr2c acts in these neurons to promote food intake and counteract the anorectic effect of serotonergic appetite suppressants. Furthermore, Htr2c marks a subset of Sim1 neurons in the paraventricular nucleus of the hypothalamus (PVH). Chemogenetic activation of these neurons in adult mice suppresses hunger, whereas their silencing promotes feeding. In support of an orexigenic role of PVH Htr2c, whole-cell patch-clamp experiments demonstrate that activation of Htr2c inhibits PVH neurons. Intriguingly, this inhibition is due to Gαi/o-dependent activation of ATP-sensitive K+ conductance, a mechanism of action not identified previously in the mammalian nervous system.
Pubmed ID: 34788630 RIS Download
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- Anti-Gq/11alpha, CT (RRID:AB_310221)
- Rabbit Anti-Green Fluorescent Protein (GFP) Polyclonal Antibody, Unconjugated (RRID:AB_221570)
- goat polyclonal anti-c-Fos (RRID:AB_2629503)
- Tyrosine Hydroxylase antibody - Neuronal Marker (RRID:AB_297840)
- AVP Polyclonal Antibody (RRID:AB_11003086)
- Rabbit Anti-Oxytocin Polyclonal Antibody, Unconjugated (RRID:AB_302818)
Associated grants
- Agency: NIDA NIH HHS, United States
Id: P50 DA033935 - Agency: NIDDK NIH HHS, United States
Id: R01 DK088423 - Agency: NIDDK NIH HHS, United States
Id: R01 DK114036
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PRISM (tool)
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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
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View all literature mentionsAnti-Gq/11alpha, CT (antibody)
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This polyclonal targets Gq/11alpha CT
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RRID:AB_221570
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