Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Avenida Camilo José Cela, 1013071 Ciudad Real, Spain.
Neuroscience. 2011 Dec 29;199:133-42. doi: 10.1016/j.neuroscience.2011.09.045. Epub 2011 Sep 29.
Pregnant rats were treated daily with 1 g/L of L-glutamate in their drinking water during pregnancy and/or lactation. The effect on adenosine A₁ receptor (A₁R) and A(2A) receptor (A(2A)R) in brains from both mothers and 15-day-old neonates was assayed using radioligand binding and real time PCR assays. Mothers receiving L-glutamate during gestation, lactation, and throughout gestation and lactation showed a significant decrease in total A₁R number (water+water, 302±49 fmol/mg; L-glutamate+water, 109±11 fmol/mg, P<0.01; water+L-glutamate, 52±13 fmol/mg, P<0.01; L-glutamate+L-glutamate, 128±33 fmol/mg, P<0.05). No variations were detected in the Kd parameter. Concerning adenosine A(2A)R, radioligand binding assays revealed that Bmax parameter remains unaltered in maternal brain in response to glutamate exposure. However, Kd parameter was significantly decreased in all L-glutamate-treated groups (water+water, 5.3±1.3 nM; L-glutamate±water, 0.5±0.1 nM; water+L-glutamate, 0.9±0.1 nM; L-glutamate±L-glutamate, 0.7±0.1 nM, P<0.01 in all cases). In both male and female neonates, A₁R was also decreased after long-term glutamate exposure during gestation, lactation, and gestation plus lactation (male neonates: water+water, 564±68 fmol/mg; L-glutamate+water, 61±8 fmol/mg; water+L-glutamate, 95±20 fmol/mg; L-glutamate+L-glutamate, 111±15 fmol/mg; P<0.01 in all cases; female neonates: water+water, 216±35 fmol/mg; L-glutamate+water, 59±9 fmol/mg; water+L-glutamate, 139±16 fmol/mg; L-glutamate+L-glutamate, 97±14 fmol/mg; P<0.01 in all cases). No variations were found in mRNA level coding adenosine A(1)R in maternal or neonatal brain. Concerning adenosine A(2A)R, radioligand binding assays revealed that Bmax parameter was significantly increased in male and female neonates exposed to L-glutamate during lactation (male neonates: water+water, 214±23 fmol/mg; water+L-glutamate, 581±49 fmol/mg; P<0.01; female neonates: water+water, 51±10 fmol/mg; water+L-glutamate, 282±52 fmol/mg; P<0.05). No variations were found in mRNA level coding adenosine A(2A)R in maternal or neonatal brain. In summary, long-term L-glutamate treatment during gestation and lactation promotes a significant down-regulation of A₁R in whole brain from both mother and neonates and a significant up-regulation of A(2A)R in neonates exposed to L-glutamate during lactation.
在妊娠和/或哺乳期，给怀孕的老鼠喂食 1g/L 的 L-谷氨酸盐作为饮用水。使用放射性配体结合和实时 PCR 检测方法检测来自母亲和 15 日龄新生大鼠大脑中的腺苷 A₁ 受体（A₁R）和 A(2A) 受体（A(2A)R）的影响。接受妊娠、哺乳期和整个妊娠及哺乳期 L-谷氨酸盐的母亲显示总 A₁R 数量显著减少（水+水，302±49 fmol/mg；L-谷氨酸盐+水，109±11 fmol/mg，P<0.01；水+L-谷氨酸盐，52±13 fmol/mg，P<0.01；L-谷氨酸盐+L-谷氨酸盐，128±33 fmol/mg，P<0.05）。Kd 参数没有变化。关于腺苷 A(2A)R，放射性配体结合试验显示，母体脑对谷氨酸暴露的 Bmax 参数保持不变。然而，所有 L-谷氨酸盐处理组的 Kd 参数均显著降低（水+水，5.3±1.3 nM；L-谷氨酸盐+水，0.5±0.1 nM；水+L-谷氨酸盐，0.9±0.1 nM；L-谷氨酸盐+L-谷氨酸盐，0.7±0.1 nM，所有情况下均 P<0.01）。在雄性和雌性新生大鼠中，在妊娠、哺乳期以及妊娠加哺乳期期间长期暴露于谷氨酸盐后，A₁R 也减少（雄性新生大鼠：水+水，564±68 fmol/mg；L-谷氨酸盐+水，61±8 fmol/mg；水+L-谷氨酸盐，95±20 fmol/mg；L-谷氨酸盐+L-谷氨酸盐，111±15 fmol/mg；所有情况下均 P<0.01；雌性新生大鼠：水+水，216±35 fmol/mg；L-谷氨酸盐+水，59±9 fmol/mg；水+L-谷氨酸盐，139±16 fmol/mg；L-谷氨酸盐+L-谷氨酸盐，97±14 fmol/mg；所有情况下均 P<0.01）。母体或新生大鼠脑腺苷 A(1)R 编码的 mRNA 水平没有变化。关于腺苷 A(2A)R，放射性配体结合试验显示，在哺乳期暴露于 L-谷氨酸盐的雄性和雌性新生大鼠的 Bmax 参数显著增加（雄性新生大鼠：水+水，214±23 fmol/mg；水+L-谷氨酸盐，581±49 fmol/mg；P<0.01；雌性新生大鼠：水+水，51±10 fmol/mg；水+L-谷氨酸盐，282±52 fmol/mg；P<0.05）。母体或新生大鼠脑腺苷 A(2A)R 编码的 mRNA 水平没有变化。总之，妊娠和哺乳期期间长期 L-谷氨酸盐治疗可显著下调母鼠和新生大鼠全脑的 A₁R，并上调哺乳期暴露于 L-谷氨酸盐的新生大鼠的 A(2A)R。
