A Buttery Taste to Vascular Biology
Endothelial Cells Generate and Release γ-Aminobutyric Acid
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γ-Aminobutyric acid (GABA), a decarboxylation product of glutamic acid, is the main inhibitory neurotransmitter in the central nervous system. It is released from presynaptic vesicles into the extracellular or synaptic space, where it mediates its effects through 2 classes of receptors (type A und type B).1,2 GABA A receptors are ligand-gated anion channels and, thus, ionotropic receptors. GABA B receptors, in contrast, are metabotropic G-protein-coupled receptors that couple to Ca2+ and K+ channels (and other signaling cascades). GABA A receptors are the targets of such important drugs like benzodiazepines, barbiturates, or ethanol, GABA B receptors are activated by baclofen.2
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Although GABA is mainly associated with its effect in the central nervous system, numerous reports suggest that GABA is also of importance in the gastrointestinal tract, the immune system, and some stem cell populations. In the gastrointestinal tract, GABA is present predominantly in interneurons of the enteric nervous system, but also epithelial cells contain a GABA system.3 L-glutamic acid decarboxylase (GAD), the enzyme producing GABA in the central nervous system, is expressed (among other tissues) in the pancreas,4 the liver, the oviduct, and some immune cells. Immune cells also express GABA transporters and receptors. Through this, GABA elicits a receptor-dependent inhibitory effect on cytokine production and immune cell proliferation.5–7
Although GABA mostly acts as an inhibitory neurotransmitter through cellular depolarization, this GABA A receptor–dependent effect requires low intracellular chloride concentrations. In cells expressing high amounts of the Na/K/2Cl- transporter, activation of GABA A results in chloride efflux and, thus, depolarization. For example, although GABA hyperpolarizes pancreatic α-cells, it depolarizes β-cells. …