Endothelial GABA signaling: a phoenix awakened

Choi, Yong Kee; Vasudevan, Anju

doi:10.18632/aging.101457

Cited by 2 publications

(1 citation statement)

References 8 publications

(9 reference statements)

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“…GABAergic signaling within the neurovascular unit (NVU) has also been described in non-neuronal cells, including astrocytes [ 12 , 13 ] and cerebrovascular endothelial cells [ 14 ]. Cortical microvessels, as well as perivascular astrocytes, receive an extensive GABAergic input from local GABA interneurons [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

GABAA and GABAB Receptors Mediate GABA-Induced Intracellular Ca2+ Signals in Human Brain Microvascular Endothelial Cells

Negri

Scolari²,

Vismara³

et al. 2022

Cells

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Numerous studies recently showed that the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), can stimulate cerebral angiogenesis and promote neurovascular coupling by activating the ionotropic GABAA receptors on cerebrovascular endothelial cells, whereas the endothelial role of the metabotropic GABAB receptors is still unknown. Preliminary evidence showed that GABAA receptor stimulation can induce an increase in endothelial Ca2+ levels, but the underlying signaling pathway remains to be fully unraveled. In the present investigation, we found that GABA evoked a biphasic elevation in [Ca2+]i that was initiated by inositol-1,4,5-trisphosphate- and nicotinic acid adenine dinucleotide phosphate-dependent Ca2+ release from neutral and acidic Ca2+ stores, respectively, and sustained by store-operated Ca2+ entry. GABAA and GABAB receptors were both required to trigger the endothelial Ca2+ response. Unexpectedly, we found that the GABAA receptors signal in a flux-independent manner via the metabotropic GABAB receptors. Likewise, the full Ca2+ response to GABAB receptors requires functional GABAA receptors. This study, therefore, sheds novel light on the molecular mechanisms by which GABA controls endothelial signaling at the neurovascular unit.

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