ArticleAmerican journal of respiratory cell and molecular biology2011
Gi-coupled γ-aminobutyric acid-B receptors cross-regulate phospholipase C and calcium in airway smooth muscle.
Article in American journal of respiratory cell and molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
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- GABA signalling in human pancreatic islets.Frontiers in endocrinology · 2023Review
- Anxiolytics for Bronchodilation: Refinements to GABAAmerican journal of respiratory cell and molecular biology · 2022Article
- Melatonin MTAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
- Endothelial GABBR2 Regulates Post-ischemic Angiogenesis by Inhibiting the Glycolysis Pathway.Frontiers in cardiovascular medicine · 2021Article
- The short-chain free fatty acid receptor FFAR3 is expressed and potentiates contraction in human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Class C GPCRs in the airway.Current opinion in pharmacology · 2020Review
- Article
- The Lactate Receptor HCAR1 Modulates Neuronal Network Activity through the Activation of GThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- The free fatty acid receptor 1 promotes airway smooth muscle cell proliferation through MEK/ERK and PI3K/Akt signaling pathways.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Signaling Mechanism of Cannabinoid Receptor-2 Activation-Induced β-Endorphin Release.Molecular neurobiology · 2016Article
- Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- GABA(B) receptors couple to Gαq to mediate increases in voltage-dependent calcium current during development.Journal of neurochemistry · 2015Article
- GABAB receptors are expressed in human aortic smooth muscle cells and regulate the intracellular Ca(2+) concentration.Heart and vessels · 2015Article
- GABAB receptors expressed in human aortic endothelial cells mediate intracellular calcium concentration regulation and endothelial nitric oxide synthase translocation.BioMed research international · 2014Article
- Hexane Fractions of Bupleurum falcatum L. Stimulates Glucagon-Like Peptide-1 Secretion through G β γ -Mediated Pathway.Evidence-based complementary and alternative medicine : eCAM · 2014Article
- Airway smooth muscle in airway reactivity and remodeling: what have we learned?American journal of physiology. Lung cellular and molecular physiology · 2013Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system, and exerts its actions via both ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors. Although the functional expression of GABA(B) receptors coupled to the G(i) protein was reported for airway smooth muscle, the role of GABA(B) receptors in airway responsiveness remains unclear. We investigated whether G(i)-coupled GABA(B) receptors cross-regulate phospholipase C (PLC), an enzyme classically regulated by G(q)-coupled receptors in human airway smooth muscle cells. Both the GABA(B)-selective agonist baclofen and the endogenous ligand GABA significantly increased the synthesis of inositol phosphate, whereas GABA(A) receptor agonists, muscimol, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol exerted no effect. The baclofen-induced synthesis of inositol phosphate and transient increases in [Ca(2+)](i) were blocked by CGP35348 and CGP55845 (selective GABA(B) antagonists), pertussis toxin (PTX, which inactivates the G(i) protein), gallein (a G(βγ) signaling inhibitor), U73122 (an inhibitor of PLC-β), and xestospongin C, an inositol 1,4,5-triphosphate receptor blocker. Baclofen also potentiated the bradykinin-induced synthesis of inositol phosphate and transient increases in [Ca(2+)](i), which were blocked by CGP35348 or PTX. Moreover, baclofen potentiated the substance P-induced contraction of airway smooth muscle in isolated guinea pig tracheal rings. In conclusion, the stimulation of GABA(B) receptors in human airway smooth muscle cells rapidly mobilizes intracellular Ca(2+) stores by the synthesis of inositol phosphate via the activation of PLC-β, which is stimulated by G(βγ) protein liberated from G(i) proteins coupled to GABA(B) receptors. Furthermore, crosstalk between GABA(B) receptors and G(q)-coupled receptors potentiates the synthesis of inositol phosphate, transient increases in [Ca(2+)](i), and smooth muscle contraction through G(i) proteins.
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