Expression of GABAA Receptor Subunits α1 and β2 in Healthy Human Dental Pulp
Abstract
BACKGROUND: Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the mammalian central nervous system (CNS), has a well-established role in pain modulation. While numerous studies have delved into the expression of GABA and its receptors in dental pulp, the exact influence of these receptors on dental pain signaling has not been fully elucidated. This study aimed to investigate the gene and protein expression of the two most abundantly expressed GABA type A (GABAA) receptor subunits, GABAA receptor subunit α1 (GABRA1) and β2 (GABRB2), in healthy human dental pulp.
METHODS: Six tooth samples were collected from healthy individuals referred for orthodontic treatment. Total RNA was isolated from the pulp tissues of three samples and reverse transcription-polymerase chain reaction (RT-PCR) was performed to assess gene expression of GABRA1 and GABRB2. The other three samples were examined using immunohistochemistry (IHC) for visualization of GABRA1 and GABRB2 proteins within the dental pulp.
RESULTS: RT-PCR analysis reported the presence of both GABRA1 and GABRB2 in the dental pulp, and independent t-test analysis revealed that the expression of GABRA1 was significantly higher than GABRB2. The immunohistochemical staining provided compelling visual evidence of the expression of GABRA1 and GABRB2 proteins within the odontoblast layer of dental pulp, clearly indicating their presence in the cell bodies and odontoblastic processes extending into the dentin.
CONCLUSION: The presence of α1 and β2 subunits of the GABAA receptor in healthy human dental pulp offers valuable insights for further research into the potential roles of GABAA receptors in dental pain signaling.
KEYWORDS: γ-aminobutyric acid, GABAA receptors, GABRA1, GABRB2, dental pain, pain signaling
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Yu C, Abbott PV. An overview of the dental pulp: Its functions and responses to injury. Aust Dent J. 2007; 52(Suppl 1): S4–6, CrossRef.
Ghannam MG, Alameddine H, Bordoni B. Anatomy, Head and Neck, Pulp (Tooth). Treasure Island: StatPearls Publishing; 2023, NLMID.
Zhan C, Huang M, Yang X, Hou J. Dental nerves: A neglected mediator of pulpitis. Int Endod J. 2021; 54(1): 85–99, CrossRef.
Sandra F, Sutanto A, Wulandari W, Lambertus R, Celinna M, Dewi NM, et al. Crucial triad in pulp-dentin complex regeneration: Dental stem cells, scaffolds, and signaling molecules. Indones Biomed J. 2023; 15(1): 25–46, CrossRef.
Sudiono J, Hardina M. The effect of Myrmecodia pendans ethanol extract on inflamed pulp: Study on sprague dawley rats. Mol Cell Biomed Sci. 2019; 3(2): 115–21, CrossRef.
Hossain MZ, Bakri MM, Yahya F, Ando H, Unno S, Kitagawa J. The role of transient receptor potential (TRP) channels in the transduction of dental pain. Int J Mol Sci. 2019; 20(3): 526, CrossRef.
Badral B, Davies AJ, Kim YH, Ahn JS, Hong SD, Chung G, et al. Pain fiber anesthetic reduces brainstem fos after tooth extraction. J Dent Res. 2013; 92(11): 1005–10, CrossRef.
Quiding H, Jonzon B, Svensson O, Webster L, Reimfelt A, Karin A, et al. TRPV1 antagonistic analgesic effect: A randomized study of AZD1386 in pain after third molar extraction. Pain. 2013; 154(6): 808–12, CrossRef.
Ghit A, Assal D, Al-Shami AS, Hussein DEE. GABAA receptors: Structure, function, pharmacology, and related disorders. J Genet Eng Biotechnol. 2021; 19: 123, CrossRef.
Baumann SW, Baur R, Sigel E. Subunit arrangement of γ-aminobutyric acid type a receptors. J Biol Chem. 2001; 276(39): 36275–80, CrossRef.
Baumann SW, Baur R, Sigel E. Forced subunit assembly in α1β2γ2 GABAA receptors: Insight into the absolute arrangement. J Biol Chem. 2002; 277(48): 46020–5, CrossRef.
Kim JH, Jeon M, Song JS, Lee JH, Choi BJ, Jung HS, et al. Distinctive genetic activity pattern of the human dental pulp between deciduous and permanent teeth. PLoS One. 2014; 9(7): e102893, CrossRef.
Kim SH, Kim S, Shin Y, Lee HS, Jeon M, Kim SO, et al. Comparative gene expression analysis of the coronal pulp and apical pulp complex in human immature teeth. J Endod. 2016; 42(5): 752–9, CrossRef.
Yuan A, Wu P, Zhong Z, He Z, Li W. Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis. J Orthop Surg Res. 2022; 17: 304, CrossRef.
Pan Q, Cai T, Veluchamy A, Hebert HL, Zhu P, Haque M, et al. A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N=221,127). MedRxiv. 2023; 2023: 2023.09.20.23295811, CrossRef.
Forsström S, Jackson CB, Carroll CJ, Kuronen M, Pirinen E, Pradhan S, et al. Fibroblast growth factor 21 drives dynamics of local and systemic stress responses in mitochondrial myopathy with mtDNA deletions. Cell Metab. 2019; 30(6): 1040–54.e7, CrossRef.
Crider A, Pandya CD, Peter D, Ahmed AO, Pillai A. Ubiquitin-proteasome dependent degradation of GABAAα1 in autism spectrum disorder. Mol Autism. 2014; 5: 45, CrossRef.
Sarang SS, Plotkin MD, Gullans SR, Cummings BS, Grant DF, Schnellmann RG. Identification of the γ-aminobutyric acid receptor β2 and β3 subunits in rat, rabbit, and human kidneys. J Am Soc Nephrol. 2001; 12(6): 1107–13, CrossRef.
Shimizu-Okabe C, Kobayashi S, Kim J, Kosaka Y, Sunagawa M, Okabe A, et al. Developmental formation of the GABAergic and glycinergic networks in the mouse spinal cord. Int J Mol Sci. 2022; 23(2):834, CrossRef.
Sieghart W, Sperk G. Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr Top Med Chem. 2002; 2(8): 795–816, CrossRef.
Everington EA, Gibbard AG, Swinny JD, Seifi M. Molecular characterization of GABA-A receptor subunit diversity within major peripheral organs and their plasticity in response to early life psychosocial stress. Front Mol Neurosci. 2018; 11: 18, CrossRef.
Zhang W, Liu QY, Haqqani AS, Leclerc S, Liu Z, Fauteux F, et al. Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human. Fluids Barriers CNS. 2020; 17(1): 47, CrossRef.
Du X, Hao H, Yang Y, Huang S, Wang C, Gigout S, et al. Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission. J Clin Investig. 2017; 127(5): 1741–56, CrossRef.
Hao H, Ramli R, Wang C, Liu C, Shah S, Mullen P, et al. Dorsal root ganglia control nociceptive input to the central nervous system. PLoS Biol. 2023; 21(1): e3001958, CrossRef.
Ramli R, Ghani N, Taib H, Baharin NHM. Successful management of dentin hypersensitivity: A narrative review. Dent Med Probl. 2022; 59(3): 451–60, CrossRef.
DOI: https://doi.org/10.18585/inabj.v16i1.2742
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