Goodyer P R, Mills M, Scriver C R
Biochim Biophys Acta. 1982 Jun 16;716(3):348-57. doi: 10.1016/0304-4165(82)90027-7.
Substantial synthesis of gamma-aminobutyric acid occurs in rat renal cortex. Renal glutamate decarboxylase activity (24.3 +/- 2.9 (S.E.) nmols/mg protein per h) is 15% of that in brain; renal gamma-aminobutyric acid content (39.5 +/- 5.3 (S.E.) nmols/g wet wt.) is 5% of the whole brain concentration. Properties of glutamate decarboxylase were studied in homogenates of rat renal cortex and rat brain under conditions for which gamma-aminobutyric acid formation from [2,3-3H]glutamate and CO2 release from [1(-14)C]glutamate were equal. Several properties of renal glutamate decarboxylase distinguish it from the corresponding brain enzyme: (1) renal glutamate decarboxylase is selectively inhibited by cysteine sulfinic acid (Ki = 5X10(-5) M); (2) renal glutamate decarboxylase is less sensitive (Ki = 3-5X10(-5) M) to inhibition by aminooxyacetic acid than is the brain enzyme (Ki = 1X10(-6) M); (3) brain but not renal glutamate decarboxylase activity can be substantially stimulated in vitro by the addition of exogenous pyridoxal 5'-phosphate; (4) renal glutamate decarboxylase is significantly decreased in renal cortex from rats on a low-salt diet. Proximal tubules are enriched in glutamate decarboxylase compared to the activity in whole renal cortex or glomeruli (42, 22 and 14 nmols/mg protein per h, respectively). We speculate that renal gamma-aminobutyric acid synthesis does not reflect the presence of GABAergic renal nerves, but may serve a function in proximal tubular cells.
大鼠肾皮质中存在大量γ-氨基丁酸的合成。肾谷氨酸脱羧酶活性(24.3±2.9(标准误)nmol/mg蛋白每小时)是脑内活性的15%;肾γ-氨基丁酸含量(39.5±5.3(标准误)nmol/g湿重)是全脑浓度的5%。在使[2,3-³H]谷氨酸生成γ-氨基丁酸与[1(-¹⁴)C]谷氨酸释放二氧化碳相等的条件下,对大鼠肾皮质和大鼠脑的匀浆中谷氨酸脱羧酶的性质进行了研究。肾谷氨酸脱羧酶的几个性质使其与相应的脑酶有所区别:(1)肾谷氨酸脱羧酶被半胱氨酸亚磺酸选择性抑制(Ki = 5×10⁻⁵ M);(2)肾谷氨酸脱羧酶对氨氧基乙酸抑制的敏感性较低(Ki = 3 - 5×10⁻⁵ M),而脑酶对其敏感性较高(Ki = 1×10⁻⁶ M);(3)体外添加外源性磷酸吡哆醛可显著刺激脑谷氨酸脱羧酶活性,但对肾谷氨酸脱羧酶无此作用;(4)低盐饮食大鼠的肾皮质中肾谷氨酸脱羧酶活性显著降低。与整个肾皮质或肾小球中的活性相比,近端小管中谷氨酸脱羧酶含量丰富(分别为42、22和14 nmol/mg蛋白每小时)。我们推测,肾γ-氨基丁酸的合成并不反映肾内存在γ-氨基丁酸能神经,但其可能在近端小管细胞中发挥作用。