Wee E L, Zimmerman E F
Neurochem Res. 1985 Dec;10(12):1673-88. doi: 10.1007/BF00988609.
To obtain further evidence that the inhibitory neurotransmitter GABA functions in palate development, the presence of an active GABA uptake mechanism was sought using primary cultures of embryonic palate mesenchymal cells. Uptake was compared from cells of two inbred mouse strains in which the SWV strain shows greater sensitivity than the AJ strain to effects of GABA on palate morphogenesis and of diazepam in producing cleft palate. Palate cells were capable of accumulating [3H]GABA by saturable uptake mechanisms characteristic of a high and low affinity active transport as indicated by temperature, Na+ ion and carrier dependence as well as Km and Vmax values that were comparable to other biological systems. The Vmax of the high-affinity uptake system from cells of the SWV strain was 1.8 fold higher than that of the AJ. GABA uptake was also observed in fibroblasts from various sources including embryonic mouse limb cells, human skin fibroblasts and 3T3 cells. When active GABA uptake was measured in skin fibroblasts from the mouse SWV and AJ strains, the rate of uptake from SWV cells under high affinity conditions was also 1.8 fold greater than in AJ cells. Thus active GABA uptake appears to be genetically regulated in non-neural cells which may contribute to differential responses to GABA.
为了获得进一步的证据证明抑制性神经递质γ-氨基丁酸(GABA)在腭部发育中发挥作用,研究人员利用胚胎腭间充质细胞的原代培养来探寻活跃的GABA摄取机制。研究人员比较了两种近交系小鼠品系细胞的摄取情况,其中SWV品系对GABA对腭部形态发生的影响以及地西泮导致腭裂的作用比AJ品系更为敏感。腭部细胞能够通过可饱和摄取机制积累[3H]GABA,这种机制具有高亲和力和低亲和力主动转运的特征,温度、Na+离子和载体依赖性以及Km和Vmax值表明其与其他生物系统相当。SWV品系细胞的高亲和力摄取系统的Vmax比AJ品系高1.8倍。在包括胚胎小鼠肢体细胞、人皮肤成纤维细胞和3T3细胞在内的各种来源的成纤维细胞中也观察到了GABA摄取。当测量小鼠SWV和AJ品系皮肤成纤维细胞中的活跃GABA摄取时,在高亲和力条件下SWV细胞的摄取速率也比AJ细胞高1.8倍。因此,活跃的GABA摄取似乎在非神经细胞中受到基因调控,这可能导致对GABA的不同反应。