Analysis of GABAA‐ and GABAB‐receptor mediated effects on intracellular Ca2+ in DRG hybrid neurones

Yokogawa, Tomonori; Kim, Seung Up; Krieger, Charles; Puil, E.

doi:10.1038/sj.bjp.0704244

“…Therefore, our findings indicate that GABA activates the GABA A receptor and subsequently inhibits α-MSH-induced melanogenesis by inhibiting intracellular Ca 2+ levels. However, a previous study revealed that GABA transiently upregulated intracellular Ca 2+ levels in mouse dorsal root ganglion neurons through high voltage-activated channels, and a GABA A receptor antagonist, (+)-bicuculline, antagonized the GABA-induced increase in intracellular Ca 2+ [ 37 ]. In contrast, Mestdagh and Wűlfert [ 38 ] determined that (+)-bicuculline increased Ca 2+ transients in cerebellar granule cells through non-GABA A receptor-associated mechanisms [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABAA and GABAB Receptors

Molagoda

¹

,

Kavinda

²

,

Ryu

³

et al. 2021

IJMS

View full text Add to dashboard Cite

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 (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 mediated 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.

show abstract

“…This may lead to increased calcium influx through voltage-gated calcium channels, which ultimately depend on the chloride transport system [ 91 ], or by depolarization due to an increase in the external potassium concentrations. It was suspected that this might lead to calcium influx through voltage activated calcium channels [ 92 ]. However, nifedipine does not affect calcium channel mediation of initial response to NA [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

Sm¹,

Ra²,

Alghzewi³

et al. 2007

View full text Add to dashboard Cite

Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group). One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine); two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil); four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups). Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility) when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect). This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

show abstract

“…This may lead to increased calcium influx through voltagegated calcium channels, which ultimately depend on the chloride transport system [91], or by depolarization due to an increase in the external potassium concentrations. It was suspected that this might lead to calcium influx through voltage activated calcium channels [92]. However, nifedipine does not affect calcium channel mediation of initial response to NA [93].…”

Section: Discussionmentioning

confidence: 99%

Effects of calcium channel blockers on antidepressant action of Alprazolam and Imipramine

Sm

¹

,

Ra

²

,

Alghzewi

³

et al. 2007

Libyan Journal of Medicine

View full text Add to dashboard Cite

Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group). One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine); two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil); four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups). Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility) when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect). This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

show abstract

Analysis of GABA_A‐ and GABA_B‐receptor mediated effects on intracellular Ca²⁺ in DRG hybrid neurones

Abstract: 1 Using pharmacological analysis and fura-2 spectro¯uorimetry, we examined the e ects of gaminobutyric acid (GABA)

Cited by 9 publications

References 52 publications

Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABAA and GABAB Receptors

Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABAA and GABAB Receptors

Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

Effects of calcium channel blockers on antidepressant action of Alprazolam and Imipramine

Contact Info

Product

Resources

About