The relative order of IP3 sensitivity of types 1 and 3 IP3 receptors is pH dependent
The relative order of IP3 sensitivity of types 1 and 3 IP3 receptors is pH dependent
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DOI：
10.1007/s004240050893
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发表时间：
1999-07-01
影响因子：
4.5
通讯作者：
Missiaen, L
中科院分区：
文献类型：
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作者：
De Smet, P;Parys, JB;Missiaen, L
与1型IP3受体(IP3R)不同，3型肌醇1，4，5-三磷酸(IP3)受体不受巯基氧化刺激，对5‘-三磷酸腺苷不敏感。在本研究中，我们比较了pH对表达IP(3)R3的16HBE140-细胞和表达IP(3)R1的A7r5细胞由IP3诱导的钙释放和细胞内钙离子的影响。PH从6.8到7.5使IP(3)R3(EC50)半最大刺激所需的IP3浓度降低了10.7倍(从2.14到0.20微米)。同样的碱化只使刺激IP(3)R1的IP3浓度(EC50)降低2.5倍(从0.87降至0.35微米)。因此，IP(3)R3在pH 6.8时是更敏感的异构体，而IP(3)R3在pH 7.5时更敏感。在pH 6.8和7.5条件下，低钙和高钙分别刺激和抑制IP(3)R1和-3。增加[H+]使IP(3)R3的钙激活曲线向高[Ca2+]方向移动，但不影响IP(3)R3的钙依赖性。我们得出结论：IP(3)、R1和-3对质子的响应明显不同。
The type-3 inositol 1,4,5-trisphosphate (IP3) receptor, in contrast to the type-1 IP3 receptor (IP3R), is not stimulated by sulfhydryl oxidation and is less sensitive to adenosine 5'-triphosphate. In the present study we compared the effect of pH on the Ca2+ release induced by IP3 and cytosolic Ca2+ between IP(3)R3-expressing 16HBE14o- cells and IP(3)R1-expressing A7r5 cells. Changing pH from 6.8 to 7.5 decreased the IP3 concentration required for half-maximal stimulation of IP(3)R3 (EC50) 10.7-fold (from 2.14 to 0.20 mu M). Similar alkalinization decreased the IP3 concentration (EC50) for stimulation of IP(3)R1 only 2.5-fold (from 0.87 to 0.35 mu M). IP(3)R1 is therefore the more sensitive isoform at pH 6.8, while IP(3)R3 is more sensitive at pH 7.5. Stimulation and inhibition of IP(3)R1 and -3 by low and high cytosolic [Ca2+] respectively was observed at both pH 6.8 and 7.5. increasing [H+] shifted the Ca2+-activation curve of IP(3)R1 towards higher [Ca2+] but did not affect the Ca2+ dependence of IP(3)R3. We conclude that IP(3)R1 and -3 differ markedly in their response to protons.