H3

2022-01-25 links: Histamine GPCR reference:

• https://mybiohack.com/blog/histamine-h3r-receptor-agonists-genetics-antagonists

H3 #

• Gi-coupled presynaptic autoreceptors. Found exclusively in CNS/PNS cells.
  • Binding levels:
    1. Pars Reticula
    2. Nucleus accumbens
    3. Striatum
    4. Globus pallidus
    5. Pars Compacta
    6. Substantia Nigra
  • mRNA signal intensity:
    1. Striatum
    2. Nucleus accumbens
    3. Subthalamic Nucleus
    4. Substantia Nigra
    5. Globus pallidus
• Decreases Acetylcholine (and increases AChE), Serotonin and Adrenaline neurotransmitter release in CNS.
• Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories
  • H3 inverse agonist enhances memory retrieval in humans
• New procognitive enhancers acting at the histamine H3 and AMPA receptors reverse natural forgetting in mice: comparisons with donepezil and memantine in the object recognition task Drugs are called S3809 and S47445 respectively.
• Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans
• Histamine Excites Striatal Dopamine D1 and D2 Receptor-Expressing Neurons via Postsynaptic H1 and H2 Receptors H3 upregulates D1

Heteromers #

• [Heteroreceptor Complexes Formed by Dopamine D 1, Histamine H 3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer’s Disease]
  • Forms heteromers with D1.
  • D1 or H3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits.. D1-H3-NMDAR complexes were confirmed.
  • H3 receptor antagonists reverted the toxicity induced by Aβ-42-amyloid peptide.
• [The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons]
  • H3 agonist treatment did not detectably alter extracellular DA levels or signaling through the cAMP/DARPP-32 signaling pathway in either D1- or D2-expressing striatal medium spiny neurons (MSNs). In D1-MSNs, H3 agonist treatment transiently activated MAPK signaling and phosphorylation of rpS6 and led to phosphorylation of GSK3β-Ser9, a novel effect
• [Dopamine D1-histamine H3 Receptor Heteromers Provide a Selective Link to MAPK Signaling in GABAergic Neurons of the Direct Striatal Pathway]
  • H3 activation stimulates p44 and p42 ERK1/2 phosphorylation only in D1-excpressing mice.
• [Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors]
  • They exhibit a Gi-dependent MAPK cascade.