Tremblay E, Ben-Ari Y, Roisin M P
Laboratoire de Neurobiologie et Physiopathologie du Développement, INSERM U29, Paris, France.
J Neurochem. 1995 Aug;65(2):863-70. doi: 10.1046/j.1471-4159.1995.65020863.x.
The effects of GABA on protein kinase C (PKC) were investigated in rat hippocampal slices at various postnatal ages [postnatal day (P) 1-P60]. At P4, GABA (300 microM) induced a rapid (in 1-2 min) 40-50% increase of PKC activity in the membrane fraction and a decrease in the cytosol. These effects were mediated by GABAB receptors because (a) they were neither blocked by 10 microM bicuculline nor reproduced by 10 microM isoguvacine and (b) they were mimicked by the GABAB agonist baclofen (3-30 microM), an effect fully antagonized by the GABAB antagonist 2-hydroxysaclofen (10 microM). A baclofen-induced increased PKC activity in the membrane fraction was only present during the early postnatal period (P1-P14); it was associated with a translocation from the cytosol to the membrane of the immunoreactivity of some PKC isoforms (alpha-, beta-, and epsilon-PKCs). In contrast, after P21, PKC activity and alpha-, beta-, epsilon-, and gamma-PKC immunoreactivities were decreased by baclofen in the membrane fraction and increased in the cytosol. These results suggest that the stimulation of GABAB receptors differentially modulates PKC activity via distinct second messenger pathways in developing and mature hippocampi.
在不同出生后年龄（出生后第1天至第60天）的大鼠海马切片中研究了γ-氨基丁酸（GABA）对蛋白激酶C（PKC）的影响。在出生后第4天，GABA（300微摩尔）诱导膜组分中PKC活性迅速（1 - 2分钟内）增加40 - 50%，而胞质溶胶中的PKC活性则降低。这些作用是由GABAB受体介导的，因为（a）它们既不被10微摩尔荷包牡丹碱阻断，也不被10微摩尔异鹅掌楸碱重现，并且（b）它们被GABAB激动剂巴氯芬（3 - 30微摩尔）模拟，而这种作用可被GABAB拮抗剂2 - 羟基 saclofen（10微摩尔）完全拮抗。巴氯芬诱导的膜组分中PKC活性增加仅在出生后早期（出生后第1天至第14天）出现；它与一些PKC亚型（α-、β-和ε-PKC）的免疫反应性从胞质溶胶向膜的转位有关。相比之下，在出生后第21天之后，巴氯芬使膜组分中的PKC活性以及α-、β-、ε-和γ-PKC免疫反应性降低，而胞质溶胶中的则增加。这些结果表明，在发育中的和成熟的海马体中，GABAB受体的刺激通过不同的第二信使途径对PKC活性进行差异调节。
