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H3-receptors control histamine release in human brain
J M Arrang1, B Devaux, J P Chodkiewicz
1Unité 109 de Neurobiologie et Pharmacologie, Centre Paul Broca de l'INSERM, Paris, France.
Journal of Neurochemistry
|July 1, 1988
Summary
Researchers found that H3-receptors regulate histamine release in the human brain. This discovery sheds light on neurotransmitter control mechanisms and potential therapeutic targets for neurological conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Neurochemistry
Background:
- Histamine plays a crucial role as a neurotransmitter in the central nervous system.
- Understanding the regulation of histamine release is vital for comprehending brain function and dysfunction.
Purpose of the Study:
- To investigate the role of H3-receptors in controlling histamine release in the human cerebral cortex.
- To determine if endogenous histamine participates in regulating its own release via H3-autoreceptors.
Main Methods:
- Utilized human cerebral cortex slices labeled with L-[3H]histidine.
- Stimulated histamine release using depolarization with increased extracellular K+ concentration.
- Assessed the effects of exogenous histamine and H3-receptor antagonists (impromidine, thioperamide) on K+-evoked release.
Main Results:
- Depolarization induced [3H]histamine release from human brain slices.
- Exogenous histamine significantly inhibited K+-evoked release, with an EC50 of 3.5 x 10(-8) M.
- H3-receptor antagonists reversed histamine's inhibitory effect and enhanced K+-evoked release, suggesting endogenous histamine involvement.
Conclusions:
- H3-receptors are confirmed to play a significant role in regulating histamine release in the human brain.
- The findings are consistent with presynaptic H3-autoreceptor control observed in rodent models.
- This study provides evidence for H3-receptor-mediated autoinhibition of histamine release in human cortical tissue.