Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> Receptors
Gamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehensively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyte-stimulating hormone (α-MSH)...
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2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/8257 |
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| author | Ilandarage Menu Neelaka Molagoda Mirissa Hewage Dumindu Kavinda Hyung Won Ryu Yung Hyun Choi Jin-Woo Jeong Sanghyuck Kang Gi-Young Kim |
| author_facet | Ilandarage Menu Neelaka Molagoda Mirissa Hewage Dumindu Kavinda Hyung Won Ryu Yung Hyun Choi Jin-Woo Jeong Sanghyuck Kang Gi-Young Kim |
| author_sort | Ilandarage Menu Neelaka Molagoda |
| collection | DOAJ |
| description | Gamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehensively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyte-stimulating hormone (α-MSH)-induced extracellular (from 354.9% ± 28.4% to 126.5% ± 16.0%) and intracellular melanin contents (from 236.7% ± 11.1% to 102.7% ± 23.1%) in B16F10 melanoma cells, without inducing cytotoxicity. In addition, α-MSH-induced hyperpigmentation in zebrafish larvae was inhibited from 246.3% ± 5.4% to 116.3% ± 3.1% at 40 mM GABA, displaying no apparent cardiotoxicity. We also clarify that the GABA-mediated antimelanogenic properties were related to the direct inhibition of microphthalmia-associated transcription factor (<i>MITF</i>) and <i>tyrosinase</i> expression by inhibiting cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Furthermore, under α-MSH stimulation, GABA-related antimelanogenic effects were mediated through the GABA<sub>A</sub> and GABA<sub>B</sub> receptors, with subsequent inhibition of Ca<sup>2+</sup> accumulation. In B16F10 melanoma cells and zebrafish larvae, pretreatment with bicuculline, a GABA<sub>A</sub> receptor antagonist, and CGP 46381, a GABA<sub>B</sub> receptor antagonist, reversed the antimelanogenic effect of GABA following α-MSH treatment by upregulating Ca<sup>2+</sup> accumulation. In conclusion, our results indicate that GABA inhibits α-MSH-induced melanogenesis. Hence, in addition to the health benefits of GABA in the central nervous system, it could ameliorate hyperpigmentation disorders. |
| first_indexed | 2024-03-10T09:14:01Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:14:01Z |
| publishDate | 2021-07-01 |
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| spelling | doaj.art-673ca78552d7439986a03aea60d96b162023-11-22T05:45:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215825710.3390/ijms22158257Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> ReceptorsIlandarage Menu Neelaka Molagoda0Mirissa Hewage Dumindu Kavinda1Hyung Won Ryu2Yung Hyun Choi3Jin-Woo Jeong4Sanghyuck Kang5Gi-Young Kim6Department of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaNatural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, KoreaDepartment of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 47227, KoreaNakdonggang National Institute of Biological Resources, Sangju 37242, KoreaKorea Beauty Industry Development Institute, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaGamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehensively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyte-stimulating hormone (α-MSH)-induced extracellular (from 354.9% ± 28.4% to 126.5% ± 16.0%) and intracellular melanin contents (from 236.7% ± 11.1% to 102.7% ± 23.1%) in B16F10 melanoma cells, without inducing cytotoxicity. In addition, α-MSH-induced hyperpigmentation in zebrafish larvae was inhibited from 246.3% ± 5.4% to 116.3% ± 3.1% at 40 mM GABA, displaying no apparent cardiotoxicity. We also clarify that the GABA-mediated antimelanogenic properties were related to the direct inhibition of microphthalmia-associated transcription factor (<i>MITF</i>) and <i>tyrosinase</i> expression by inhibiting cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Furthermore, under α-MSH stimulation, GABA-related antimelanogenic effects were mediated through the GABA<sub>A</sub> and GABA<sub>B</sub> receptors, with subsequent inhibition of Ca<sup>2+</sup> accumulation. In B16F10 melanoma cells and zebrafish larvae, pretreatment with bicuculline, a GABA<sub>A</sub> receptor antagonist, and CGP 46381, a GABA<sub>B</sub> receptor antagonist, reversed the antimelanogenic effect of GABA following α-MSH treatment by upregulating Ca<sup>2+</sup> accumulation. In conclusion, our results indicate that GABA inhibits α-MSH-induced melanogenesis. Hence, in addition to the health benefits of GABA in the central nervous system, it could ameliorate hyperpigmentation disorders.https://www.mdpi.com/1422-0067/22/15/8257GABAGABA receptormelanogenesisCa<sup>2+</sup> |
| spellingShingle | Ilandarage Menu Neelaka Molagoda Mirissa Hewage Dumindu Kavinda Hyung Won Ryu Yung Hyun Choi Jin-Woo Jeong Sanghyuck Kang Gi-Young Kim Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> Receptors International Journal of Molecular Sciences GABA GABA receptor melanogenesis Ca<sup>2+</sup> |
| title | Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> Receptors |
| title_full | Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> Receptors |
| title_fullStr | Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> Receptors |
| title_full_unstemmed | Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> Receptors |
| title_short | Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA<sub>A</sub> and GABA<sub>B</sub> Receptors |
| title_sort | gamma aminobutyric acid gaba inhibits α melanocyte stimulating hormone induced melanogenesis through gaba sub a sub and gaba sub b sub receptors |
| topic | GABA GABA receptor melanogenesis Ca<sup>2+</sup> |
| url | https://www.mdpi.com/1422-0067/22/15/8257 |
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