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Related Concept Videos

G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Regulation of Food Intake01:30

Regulation of Food Intake

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...

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Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
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Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus.

H Xu1, S Qin, G A Carrasco

  • 1Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago School of Medicine, Maywood, IL 60153, USA.

Neuroscience
|December 20, 2008
PubMed
Summary

Selective serotonin reuptake inhibitors (SSRIs) take weeks to treat mood disorders. Estradiol may accelerate SSRI effects by targeting the GPR30 receptor in the hypothalamus, potentially speeding mood disorder treatment.

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Brain Membrane Fractionation: An Ex Vivo Approach to Assess Subsynaptic Protein Localization

Published on: May 12, 2017

Area of Science:

  • Neuroendocrinology
  • Pharmacology
  • Molecular Psychiatry

Background:

  • Selective serotonin reuptake inhibitors (SSRIs) are standard treatments for mood disorders, but their therapeutic effects manifest after 1–2 weeks.
  • SSRIs function by attenuating serotonin 1A (5-HT(1A)) receptor signaling, leading to reduced oxytocin and adrenocorticotropin hormone (ACTH) release.
  • Estradiol also attenuates 5-HT(1A) receptor signaling, but its effects occur more rapidly (within 2 days in rats).

Purpose of the Study:

  • To investigate the role of the G-protein-coupled estrogen receptor, GPR30, in the hypothalamus.
  • To determine if GPR30 mediates estradiol's rapid attenuation of 5-HT(1A) receptor signaling.
  • To explore the potential of targeting GPR30 to accelerate SSRI therapeutic effects in mood disorders.

Main Methods:

  • Localization of GPR30 in the hypothalamic paraventricular nucleus (PVN) of rats using immunohistochemistry.
  • Assessment of co-localization of GPR30 with 5-HT(1A) receptors, corticotrophin-releasing factor (CRF), and oxytocin.
  • Experimental manipulation using pertussis-toxin (PTX) and selective GPR30 agonist (G-1) to evaluate effects on oxytocin and ACTH responses to a 5-HT(1A) receptor agonist.

Main Results:

  • High levels of GPR30 were found in the rat PVN, co-localizing with 5-HT(1A) receptors and key neuroendocrine hormones.
  • PTX pretreatment blocked estradiol's attenuation of the oxytocin response to 5-HT(1A) receptor stimulation.
  • Treatment with the GPR30 agonist G-1 significantly attenuated oxytocin (29%) and ACTH (31%) responses to 5-HT(1A) receptor agonist stimulation.

Conclusions:

  • The study identifies GPR30 as a putative extranuclear estrogen receptor involved in estradiol-mediated attenuation of 5-HT(1A) receptor signaling in the PVN.
  • GPR30 activation can rapidly attenuate 5-HT(1A) receptor signaling, suggesting a mechanism for accelerating SSRI effects.
  • Targeting GPR30 may offer a novel strategy to expedite the therapeutic benefits of SSRIs for mood disorders.