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GABAA and GABAB Receptors Mediate GABA-Induced Intracellular Ca2+ Signals in Human Brain Microvascular Endothelial Cells.
Negri, Sharon; Scolari, Francesca; Vismara, Mauro; Brunetti, Valentina; Faris, Pawan; Terribile, Giulia; Sancini, Giulio; Berra-Romani, Roberto; Moccia, Francesco.
Afiliación
  • Negri S; Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
  • Scolari F; Institute of Molecular Genetics (IGM)-CNR "Luigi Luca Cavalli-Sforza", 27100 Pavia, Italy.
  • Vismara M; Laboratory of Biochemistry, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
  • Brunetti V; Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
  • Faris P; Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
  • Terribile G; School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
  • Sancini G; Nanomedicine Center, Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
  • Berra-Romani R; School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
  • Moccia F; Nanomedicine Center, Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
Cells ; 11(23)2022 Nov 30.
Article en En | MEDLINE | ID: mdl-36497118
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de GABA / Células Endoteliales Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de GABA / Células Endoteliales Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza