Desensitization of calcium messenger system in parathyroid hormone-stimulated opossum kidney cells.

Desensitization of calcium messenger system in parathyroid hormone-stimulated opossum kidney cells.
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甲状旁腺激素刺激负鼠肾细胞中钙信使系统的脱敏。

DOI:
10.1152/ajpendo.1993.264.6.e918
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发表时间:
1993
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Civitelli,R
Civitelli,R
中科院分区:
--
文献类型:
--
作者:
Fujimori,A;Miyauchi,A;Hruska,KA;Martin,KJ;Avioli,LV;Civitelli,R

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我们通过监测负鼠肾细胞系 (OKP) 中的细胞内钙浓度 ([Ca2+]i) 研究了钙信息系统对甲状旁腺激素 (PTH) 的脱敏。 PTH (10(-7) M) 导致 [Ca2+]i 短暂增加,平均峰高比基线高 48.7 +/- 4.7% (n = 32)。用 10(-7) 或 10(-8) M PTH 刺激的细胞对最大剂量 (10(-7) M) 激素的第二次刺激没有反应,而较低浓度的 PTH(10(-9) M 和 10(-10) M)仅使细胞部分脱敏,因为 [Ca2+]i 瞬变幅度较小(12.7 +/- 2.1 和 40.6 +/-)第二次刺激时观察到分别高于基线 6.2%。当 PTH 受体结合没有显着降低时,初始激素暴露后 5 分钟内就会出现脱敏。仅在 2 小时后才实现 PTH 结合位点的最大减少 (37.0 +/- 1.4%)。 10(-9) M 佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 可再现部分脱敏作用,但二丁酰基腺苷 3',5'-环单磷酸不能再现部分脱敏作用,并且可被星形孢菌素阻断。但星形孢素对高剂量PTH引起的完全脱敏没有作用。在10(-9) M时,PTH还引起3',5'-环单磷酸腺苷(cAMP)反应的时间依赖性脱敏,2小时后达到最大抑制。 PMA也降低了cAMP对PTH的反应,但其抑制作用不如10(-9)M PTH有效。因此,PTH 会诱导 OKP 细胞中 Ca2+ 信息系统的剂量依赖性同源脱敏,与受体占用无关。(摘要截断为 250 字)
We have studied the desensitization of the calcium message system to parathyroid hormone (PTH) by monitoring intracellular calcium concentration ([Ca2+]i) in an opossum kidney cell line (OKP). PTH (10(-7) M) caused a transient increase in [Ca2+]i, with an average peak height of 48.7 +/- 4.7% above baseline (n = 32). Cells stimulated with either 10(-7) or 10(-8) M PTH did not respond to a second challenge with a maximal dose (10(-7) M) of the hormone, whereas lower concentrations of PTH (10(-9) M and 10(-10) M) only partially desensitized the cells, since a [Ca2+]i transient of smaller amplitude (12.7 +/- 2.1 and 40.6 +/- 6.2% above baseline, respectively) was observed with a second stimulation. Desensitization developed within 5 min of initial hormone exposure, when PTH receptor binding was not significantly decreased. Maximal reduction of PTH binding sites (37.0 +/- 1.4%) was achieved only after 2 h. Partial desensitization was reproduced by 10(-9) M phorbol 12-myristate 13-acetate (PMA) but not by dibutyryladenosine 3',5'-cyclic monophosphate, and it was blocked by staurosporine. However, staurosporine had no effect on the complete desensitization induced by high doses of PTH. At 10(-9) M, PTH also caused a time-dependent desensitization of the adenosine 3',5'-cyclic monophosphate (cAMP) response, with maximal inhibition achieved after 2 h. PMA also decreased the cAMP response to PTH, but its inhibitory effect was less potent than that of 10(-9) M PTH. Therefore PTH induces a dose-dependent homologous desensitization of the Ca2+ message system in OKP cells, independent of receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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