Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, N, Denmark.
Life Sci. 2018 Dec 1;214:145-152. doi: 10.1016/j.lfs.2018.10.033. Epub 2018 Oct 19.
γ-aminobutyric acid (GABA) mediates its physiological effects through the GABA and GABA receptors. In this study the putative expression of GABAR and GABAR subunits in human myometrium tissue was investigated.
The expression levels of the 19 GABAR subunits (α-α, β-β, γ-γ, δ, ε, π, θ, ρ-ρ) and the three GABAR subunits (GABA, GABA, GABA) were characterized by RT-qPCR analysis on two commercial samples and six samples derived from surgically removed myometrial tissues from different women. We probed for functional GABAR expression in primary human myometrial smooth muscle cells (HMSMCs) by whole-cell patch-clamp electrophysiology.
The absolute mRNA levels of the 22 GABAR and GABAR genes varied considerably across the eight samples, but a pronounced overlap existed between the specific subunits detected in the samples, with α, β, β, ε, π, θ, GABA and GABA mRNAs being detected in most samples. The expression profile of GABAR and GABAR subunit mRNAs in HMSMCs correlated with that observed in the eight tissue samples, albeit the subunit transcripts were detected at lower relative levels. Neither muscimol nor GABA evoked significant currents in these cells in the patch-clamp recordings.
While the expression of the GABA subunits on their own is unlikely to give rise to functional GABAR expression, the GABAR subunits identified at mRNA level would be able to form functional receptors in the human myometrial tissue. Although GABAR-mediated currents could not be recorded from HMSMCs in this study, this suggests a role for GABAergic transmission in the human myometrium.
γ-氨基丁酸(GABA)通过 GABA 和 GABA 受体来介导其生理作用。在这项研究中,研究了人子宫肌组织中 GABAAR 和 GABAAR 亚基的假定表达。
通过 RT-qPCR 分析两个商业样本和六个取自不同女性手术切除的子宫肌组织样本,研究了 19 个 GABAAR 亚基(α-α、β-β、γ-γ、δ、ε、π、θ、ρ-ρ)和三个 GABAAR 亚基(GABA、GABA、GABA)的表达水平。我们通过全细胞膜片钳电生理学技术在原代人子宫平滑肌细胞(HMSMCs)中探测功能性 GABAAR 表达。
在这 8 个样本中,22 个 GABAAR 和 GABAAR 基因的绝对 mRNA 水平差异很大,但在样本中检测到的特定亚基之间存在明显的重叠,大多数样本中检测到α、β、β、ε、π、θ、GABA 和 GABA mRNA。HMSMCs 中 GABAAR 和 GABAAR 亚基 mRNA 的表达谱与在 8 个组织样本中观察到的表达谱相关,尽管亚基转录本的相对水平较低。在这些细胞的膜片钳记录中,无论是 muscimol 还是 GABA 都不能引起明显的电流。
虽然单独的 GABA 亚基不太可能产生功能性 GABAAR 表达,但在 mRNA 水平上鉴定的 GABAAR 亚基将能够在人子宫肌组织中形成功能性受体。尽管在这项研究中不能从 HMSMCs 中记录到 GABAAR 介导的电流,但这表明 GABA 能传递在人子宫肌中有作用。