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[논문] Gamma-Aminobutyric Acid (GABA) Inhibits alpha-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABA(A) and GABA(B) Receptors

International Journal of Molecular Sciences

5.924

EISSN: 1422-0067

22(15)

SCIE

Gamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehenꠓsively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyteꠓstimulating 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 carꠓdiotoxicity. We also clarify that the GABA-mediated antimelanogenic properties were related to the direct inhibition of microphthalmia-associated transcription factor (MITF) and tyrosinase expression by inhibiting cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Furthermore, under α-MSH stimulation, GABA-related antimelanogenic effects were mediꠓated through the GABAA and GABAB receptors, with subsequent inhibition of Ca2+ accumulation.
In B16F10 melanoma cells and zebrafish larvae, pretreatment with bicuculline, a GABAA receptor antagonist, and CGP 46381, a GABAB receptor antagonist, reversed the antimelanogenic effect of GABA following α-MSH treatment by upregulating Ca2+ 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.

Molagoda, Ilandarage Menu Neelaka; Kavinda, Mirissa Hewage Dumindu; Ryu, Hyung Won; Choi, Yung Hyun; Jeong, Jin-Woo; Kang, Sanghyuck; Kim, Gi-Young;

2021.07.31.

https://doi.org/10.3390/ijms22158257