Acidosis inhibits 1,25-(OH)2D3 but not cAMP production in response to parathyroid hormone in the rat.
Acidosis inhibits 1,25-(OH)2D3 but not cAMP production in response to parathyroid hormone in the rat.
复制标题
酸中毒会抑制大鼠体内甲状旁腺激素响应的 1,25-(OH)2D3，但不会抑制 cAMP 的产生。
DOI：
10.1002/jbmr.5650050311
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Favus,MJ
中科院分区：
文献类型：
--
作者：
Ro,HK;Tembe,V;Krug,T;Yang,PY;Bushinsky,DA;Favus,MJ
甲状旁腺激素 (PTH) 是肾近曲小管 25-羟基维生素 D3-1-羟化酶 (1-OHase) 的主要激活剂。慢性代谢性酸中毒 (CMA) 会抑制 1-OHase 并降低低钙饮食（LCD，0.002% Ca）大鼠体内循环 1,25-二羟基维生素 D3[1,25-(OH)2D3] 水平。为了研究 CMA 抑制 1-OHase 的细胞机制，在喂食 LCD 14 天并通过在饮用水中添加 1.5% 氯化铵使其酸中毒的大鼠中分离出近端肾小管，测量 PTH 依赖性肾 1-OHase 活性和 cAMP。酸中毒大鼠血清 1,25-(OH)2D3 和近曲小管 1-OHase 活性和 cAMP 含量较低。 hPTH-(1-34) (10-7M) 体外将 CMA 大鼠和非酸中毒对照大鼠肾小管中的 cAMP 含量增加至同等浓度；然而，PTH 仅在非酸中毒动物的肾小管中增加 1-OHase 活性。尽管毛喉素可将酸中毒和非酸中毒大鼠肾小管中的 cAMP 含量增加至同等水平，但非酸中毒大鼠肾小管中 1-OHase 活性下降，而酸中毒肾小管中 1-OHase 活性仍受到抑制。结果表明，慢性代谢性酸中毒通过改变 cAMP 独立信使系统中的一个或多个步骤来抑制 1-OHase 的 PTH 激活。 PTH 和毛喉素可增加酸中毒和非酸中毒近曲小管的 cAMP 产生；然而，酸中毒小管中的 1-OHase 活性不会恢复正常，非酸中毒小管 1-OHase 可能会受到抑制。
Parathyroid hormone (PTH) is a major activator of renal proximal tubule 25‐hydroxyvitamin D3‐1‐hydroxylase (1‐OHase). Chronic metabolic acidosis (CMA) inhibits 1‐OHase and reduces circulating 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3] levels in rats fed a low‐Ca diet (LCD, 0.002% Ca). To examine the cellular mechanism whereby CMA inhibits 1‐OHase, PTH‐dependent renal 1‐OHase activity and cAMP were measured in proximal tubules isolated from rats fed LCD for 14 days and made acidotic by the addition of 1.5% ammonium chloride to the drinking water. Serum 1,25‐(OH)2D3and proximal tubule 1‐OHase activity and cAMP content were lower in acidotic rats. hPTH‐(1–34) (10−7M) in vitro increased cAMP content to equivalent concentrations in tubules from rats with CMA and from nonacidotic controls; however, PTH increased 1‐OHase activity only in tubules from nonacidotic animals. Although forskolin increased tubule cAMP content to equivalent levels in tubules from acidotic and nonacidotic rats, 1‐OHase activity declined in tubules from nonacidotic rats and remained suppressed in acidotic tubules.The results suggest that chronic metabolic acidosis inhibits the PTH activation of 1‐OHase through alteration of one or more steps in a cAMP‐independent messenger system. PTH and forskolin can increase cAMP production by acidotic and nonacidotic proximal tubules; however, 1‐OHase activity is not restored to normal in acidotic tubules and nonacidotic tubule 1‐OHase may be inhibited.