Effect of metabolic acidosis on the PTH receptor-adenylate cyclase system of canine kidney.
Effect of metabolic acidosis on the PTH receptor-adenylate cyclase system of canine kidney.
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代谢性酸中毒对犬肾PTH受体-腺苷酸环化酶系统的影响
DOI：
10.1152/ajprenal.1985.249.4.f566
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
V. Paz
中科院分区：
文献类型：
--
作者：
E. Bellorín;J. Humpierres;J. Weisinger;C. Milanés;V. Sylva;V. Paz
甲状旁腺激素(PTH)的磷酸作用在代谢性酸中毒时被钝化。以前的研究表明，在这种情况下，PTH对肾皮质腺苷环化酶的激活作用降低。然而，这种缺陷背后的机制还没有完全确定。本研究旨在探讨代谢性酸中毒犬皮层基底外侧膜上甲状旁腺激素与其受体-腺苷环化酶系统的相互作用。用7只正常犬建立慢性代谢性酸中毒模型。静脉血pH降至7.21+/-0.01，血清碳酸氢盐降至12.58+/-0.32meq/L。7只对照犬血液pH值为7.38+/-0.002，血清碳酸氢盐为20.14+/-0.26meq/L。手术摘除肾脏，以不连续的蔗糖密度梯度通过差速离心法和超速离心法制备基侧膜，以研究腺苷环化酶活性和激素受体结合。代谢性酸中毒导致甲状旁腺激素依赖性腺苷环化酶活性显著降低(对照组Vmax 2,119+/-150pmolcAMP X mg prot-1.30min-1比3,548+/-116)。给予腺苷环化酶半最大活性的甲状旁腺素浓度不变。然而，PTH受体结合在两组膜上表现出相似的亲和力和结合能力。基础酶活性也相似。在GTP类似物5‘-鸟氨酰亚胺二磷酸存在下，酸性狗膜的甲状旁腺激素依赖性腺苷酸环化酶活力仍显著低于对照组。在酸中毒犬的细胞膜上，NaF刺激酶活性的能力也受到抑制。在有Mn2+存在时，两组的酶活性相似。
The phosphaturic action of parathyroid hormone (PTH) is blunted during metabolic acidosis. Previous studies suggest that the activation of renal cortical adenylate cyclase by PTH is decreased under this condition. However, the mechanisms underlying the defect are not completely defined. The present studies were designed to examine the interaction of PTH with its receptor-adenylate cyclase system in basolateral cortical membranes from dogs with metabolic acidosis. Chronic metabolic acidosis was induced in seven normal dogs. Venous blood pH decreased to 7.21 +/- 0.01 and serum bicarbonate to 12.58 +/- 0.32 meq/liter. In seven control dogs blood pH was 7.38 +/- 0.002 and serum bicarbonate was 20.14 +/- 0.26 meq/liter. The kidneys were surgically removed and basolateral membranes were prepared by differential centrifugation and ultracentrifugation in discontinuous sucrose density gradients for studies of adenylate cyclase activity and hormone-receptor binding. Metabolic acidosis resulted in a significant decrease in PTH-dependent adenylate cyclase activity (Vmax 2,119 +/- 150 pmol cAMP X mg prot-1 .30 min-1 vs. 3,548 +/- 116 in the controls). The PTH concentration giving half-maximal activation of adenylate cyclase was unchanged. However, PTH-receptor binding showed similar affinity and binding capacity in both groups of membranes. Basal enzyme activity was also similar. In the presence of the GTP analogue 5'-guanylylimidodiphosphate, PTH-dependent adenylate cyclase activity remained markedly decreased in the acidotic dog membranes compared with the controls. The ability of NaF to stimulate enzyme activity was also depressed in the membrane of acidotic dogs. Enzyme activity in the presence of Mn2+ was similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)