Negative modulation of the GABAAρ1 receptor function by histamine

González, Andrea Natalia Beltrán; Pazos, Manuel Ignacio Lopez; Vas, Mariana del; Calvo, Daniel J.

doi:10.1016/j.ejphar.2023.175880

Cited by 1 publication

(1 citation statement)

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“…It was recently shown that histamine negatively modulates ρ1 GABA C receptors expressed in oocytes, whereas it positively modulates a range of GABA A receptors (González et al., 2023). Interestingly, opposite effects involving these receptors have been noted previously; for example, opposing roles for these receptors have been described for short‐term memory in young chicks where GABA A antagonism inhibited memory and GABA C antagonism reinforced memory (Gibbs & Johnston, 2005).…”

Section: Ionotropic Gaba Receptorsmentioning

confidence: 99%

Milestone review: GABA, from chemistry, conformations, ionotropic receptors, modulators, epilepsy, flavonoids, and stress to neuro‐nutraceuticals

Johnston,

Beart

2024

Journal of Neurochemistry

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Arising out of a PhD project more than 50 years ago to synthesise analogues of the neurotransmitter GABA, a series of new chemical entities were found to have selective actions on ionotropic GABA receptors. Several of these neurochemicals are now commercially available. A new subtype of these receptors was discovered that could be a target for the treatment of myopia, the facilitation of learning and memory, and the improvement of post‐stroke motor recovery. The development of these new chemical entities over many years demonstrates the importance of neurochemicals with which to investigate selective aspects of GABA receptors and illustrates the significance of collaboration between chemists and biologists in neurochemistry. Vital were the improvements in synthetic organic chemistry and the use of functional human receptors expressed in oocytes. Current interest in ionotropic GABA receptors includes the clinical development of subtype‐specific agents and the role of gain‐of‐function receptor variants in epilepsy. Dietary flavonoids were found to cross the blood–brain barrier to influence brain function. Natural and synthetic flavonoids had a range of effects on GABA receptors, ranging from positive, silent, and negative allosteric modulators, to even second‐order modulation of first‐order modulators. Flavonoids have been called “a new family of benzodiazepines.” Like benzodiazepines, flavonoids reduce stress. Stress produces changes in GABA receptors in the brain that may be because of changes in endogenous modulators, such as neurosteroids and corticosteroids. GABA also occurs naturally in the diet leading to studies of the effects of oral GABA on brain function. This finding has resulted in studies of GABA and related neurochemicals as neuro‐nutraceuticals. GABA systems in the gut microbiome are essential to such studies. The actions of oral GABA and of GABA‐enriched beverages and foodstuffs are now an area of considerable scientific and commercial interest. GABA is a deceptively simple chemical that can take up many shapes, which may underlie its complex functions. The need for new chemical entities with selective actions for further studies highlights the need for continuing collaboration between chemists and biologists.

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Section: Ionotropic Gaba Receptorsmentioning

confidence: 99%