Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells.
Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells.
复制标题
蛋白激酶C通过直接影响成骨性骨肉瘤细胞中的PTH受体参与PTH诱导的同源脱敏。
作者：
K. Ikeda;T. Sugimoto;M. Fukase;T. Fujita
我们研究了PTH诱导的同源脱敏机制，反映在cAMP反应的难治性的第二次暴露于PTH的克隆大鼠骨肉瘤细胞系，UMR-106。用10（-7）M大鼠（r）PTH-（1 - 34）预孵育6小时引起脱敏，导致cAMP积累减少65%，以响应进一步暴露于rPTH。这种脱敏作用在10（-10）M rPTH时明显，在10（-7）M rPTH时最大。用蛋白激酶C（PK-C）激活佛波酯12-肉豆蔻酸13-乙酸佛波酯（PMA，10（-6）M）处理UMR-106细胞6小时，也可诱导脱敏，表现为rPTH刺激的cAMP积累减少到对照细胞的50%。另一方面，不能激活PK-C的4 α-佛波醇12，13-二癸酸酯未能诱导脱敏。50微摩尔H-7（PK-C抑制剂）显著阻断rPTH和PMA诱导的脱敏。因此，PK-C似乎在rPTH诱导的脱敏中起主要作用。用rPTH或PMA预处理均不改变cAMP对10微克/毫升霍乱毒素或100 μ M毛喉素的反应性。胰岛激活蛋白对该细胞系的脱敏作用无影响。通过使用125 I标记的[Nle 8，Nle 18，Tyr 34] PTH-（1 - 34）作为放射性配体来评估PTH受体结合，通过用rPTH或PMA预处理，PTH受体结合与PTH受体数目一起沿着降低。这些数据表明，rPTH诱导的同源脱敏至少部分通过PK-C的激活发生，PK-C直接影响UMR-106细胞中的PTH受体。
We have investigated mechanisms of PTH-induced homologous desensitization reflected in the refractoriness of cAMP response to the second exposure to PTH in the clonal rat osteosarcoma cell line, UMR-106. Preincubation with 10(-7) M rat (r) PTH-(1-34) for 6 h caused the desensitization, resulting in a 65% decrease in cAMP accumulation in response to further exposure to rPTH. This desensitization was apparent at 10(-10) M rPTH and maximal at 10(-7) M rPTH. UMR-106 cells treated with protein kinase C (PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 10(-6) M) for 6 h also induced desensitization manifested by a loss of rPTH-stimulated cAMP accumulation to 50% of that in the control cells. On the other hand, 4 alpha-phorbol 12,13-didecanoate, incapable of activating PK-C, failed to induce desensitization. Fifty micromolar H-7 (PK-C inhibitor) significantly blocked both rPTH- and PMA-induced desensitization. Thus, PK-C seemed to play a major role in rPTH-induced desensitization. Pretreatment with neither rPTH nor PMA changed the cAMP responsiveness to 10 micrograms/ml cholera toxin or 100 microM forskolin. Islet activating protein failed to influence the desensitization in this cell line. PTH receptor binding, assessed by using 125I-labeled [Nle8,Nle18,Tyr34]PTH-(1-34) as a radioligand, was decreased along with PTH receptor numbers by pretreatment with rPTH or PMA. These data indicate that rPTH-induced homologous desensitization occurs at least in part through the activation of PK-C and that PK-C directly affects PTH receptor in UMR-106 cells.
登录
查看更多内容
甲状旁腺激素急剧升高成骨细胞样细胞中的细胞内钙。
DOI：
10.1152/ajpendo.1987.253.1.e45
发表时间：
1987
期刊：
The American journal of physiology
影响因子：
--
作者：
Reid,IR;Civitelli,R;Halstead,LR;Avioli,LV;Hruska,KA
通讯作者：
Hruska,KA
蛋白激酶-C 抑制剂调节负鼠肾细胞中甲状旁腺激素受体腺苷酸环化酶系统的脱敏。
影响因子：
4.8
作者：
Pernalete,N;Garcia,JC;Betts,CR;Martin,KJ
通讯作者：
Martin,KJ
佛波酯诱导火鸡红细胞中腺苷酸环化酶的脱敏和 β-肾上腺素能受体的磷酸化。
DOI：
10.1073/pnas.81.14.4316
发表时间：
1984
影响因子：
11.1
作者：
Kelleher,DJ;Pessin,JE;Ruoho,AE;Johnson,GL
通讯作者：
Johnson,GL
甲状旁腺激素及其类似物对培养的大鼠成骨样细胞胞质钙离子和 cAMP 水平的差异影响。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Donahue,HJ;Fryer,MJ;Eriksen,EF;Heath3rd,H
通讯作者：
Heath3rd,H