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Molecular and functional adaptation of the GABA A receptor complex during pregnancy and after delivery in the rat brain

1998; Wiley; Volume: 10; Issue: 9 Linguagem: Inglês

10.1111/j.1460-9568.1998.00300.x

1460-9568

Paolo Follesa, Stefania Floris, Graziella Tuligi, Maria Cristina Mostallino, Alessandra Concas, Giovanni Biggio,

Receptor Mechanisms and Signaling

Abstract The abundance of γ‐aminobutyric acid receptor type A (GABA A receptor) subunit mRNAs and polypeptides as well as muscimol‐stimulated 36 Cl – uptake were measured in rat cerebral cortex or hippocampus at various times during pregnancy and after delivery. RNase protection assays revealed that the amount of the γ2L subunit mRNA decreased progressively during pregnancy, in the cerebral cortex and hippocampus, and then returned to control values around the time of delivery. A similar pattern was observed for the α5 subunit mRNA in the cerebral cortex, whereas no significant changes were apparent for α1, α2, α3, α4, β1, β2, β3 and γ2S subunit mRNAs. The amounts of γ2 and α1 proteins in the cerebral cortex were measured by immunoblot analysis; whereas the abundance of γ2 protein decreased during pregnancy, no change was detected in the amount of α1 protein. Evaluation for functional significance of the down‐regulated γ2 and α5 subunit was made by determining the GABA A receptor function assessed by measurement of muscimol‐stimulated 36 Cl – uptake in cerebral cortical membrane vesicles. Muscimol‐induced 36 Cl – uptake was markedly reduced during of pregnancy compared with rats in oestrus. At this same time, the potentiating effects of diazepam and allopregnanolone on muscimol stimulation of 36 Cl – uptake also were reduced. In contrast, the effects of muscimol, allopregnanolone and diazepam were significantly increased, relative to animals in oestrus, after delivery.