Uusi-Oukari Mikko, Kosonen Paula, Homanics Gregg E, Korpi Esa R
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
Neurochem Res. 2004 Apr;29(4):771-80. doi: 10.1023/b:nere.0000018849.54169.c4.
We have utilized quantitative autoradiography with the GABA(A) receptor chloride channel blocker [35S]t-butylbicyclophosphorothionate ([35S]TBPS) in rodent brain sections to investigate if differential proton modulation of various GABA(A) receptor subtypes expressed in various brain regions are differentially sensitive to pH alternations. Acidic and basic pHs decreased the binding, the mean values at pH 5.4 and pH 9.4 being 17% and 76% of the binding at pH 7.4, respectively. The regional profiles of the pH effects could be divided into two types. In regions with high basal binding at pH 7.4. the pH profile was usually 'bell-shaped,' with maximal binding at pH 7.4 (type 1). In regions with low basal binding at pH 7.4, the pH profile (type 2) revealed very low binding at pH 5.4, lower sensitivity to high pH, and usually maximal binding at pH 8.4. In brain regions with type 1 pH modulation alpha1 and beta2 subunits are abundantly expressed, whereas alpha2 and beta3 subunits are abundant in type 2 regions. Therefore the alpha1beta2gamma2 and alpha2beta3gamma2 receptor subtypes are suggested to be preferentially responsible for brain regional heterogeneity of the pH modulation of [35S]TBPS binding.
我们利用定量放射自显影技术，结合γ-氨基丁酸A（GABA(A)）受体氯离子通道阻滞剂[35S]叔丁基双环磷硫代酸盐（[35S]TBPS），对啮齿动物脑切片进行研究，以探讨在不同脑区表达的各种GABA(A)受体亚型的差异质子调节是否对pH值变化具有不同的敏感性。酸性和碱性pH值均降低了结合，在pH 5.4和pH 9.4时的平均值分别为pH 7.4时结合的17%和76%。pH值效应的区域分布可分为两种类型。在pH 7.4时基础结合较高的区域，pH值分布通常呈“钟形”，在pH 7.4时结合最大（类型1）。在pH 7.4时基础结合较低的区域，pH值分布（类型2）显示在pH 5.4时结合非常低，对高pH值的敏感性较低，通常在pH 8.4时结合最大。在具有1型pH调节的脑区中，α1和β2亚基大量表达，而在2型区域中α2和β3亚基丰富。因此，α1β2γ2和α2β3γ2受体亚型被认为是[35S]TBPS结合pH调节脑区异质性的主要原因。
