Regulation of inositol trisphosphate accumulation by muscarinic cholinergic and H1-histamine receptors on human astrocytoma cells. Differential induction of desensitization by agonists.
Regulation of inositol trisphosphate accumulation by muscarinic cholinergic and H1-histamine receptors on human astrocytoma cells. Differential induction of desensitization by agonists.
复制标题
人星形细胞瘤细胞上毒蕈碱胆碱能受体和 H1-组胺受体对肌醇三磷酸积累的调节。
DOI：
10.1042/bj2410337
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Harden,TK
中科院分区：
文献类型：
--
作者：
Nakahata,N;Harden,TK
尽管在1321 N1人星形细胞瘤细胞上毒蕈碱胆碱能受体的活化导致肌醇磷酸在LiCl存在下线性积累长达60分钟[Masters，Quinn & Brown（1985）Mol. Pharmacol. 27，325-332]，H1-组胺受体的激活导致总肌醇磷酸形成的增加，其维持少于5分钟。刺激这两种受体对肌醇1，4，5-三磷酸[Ins（1，4，5）P3]、肌醇1，3，4-三磷酸[Ins（1，3，4）P3]和肌醇1，3，4，还检查了5-四磷酸[Ins（1，3，4，5）P4]。1321 N1细胞与卡巴胆碱孵育导致所有三个肌醇磷酸盐的快速积累，在30秒内达到最大值，这一升高的值维持了长达60分钟。的速度消失的Ins（1，3，4）P3从卡巴胆碱处理的细胞后，加入阿托品的抑制剂或超过的Ins（1，4，5）P3的消失率。尽管在组胺存在下Ins（1，4，5）P3、Ins（1，3，4）P3和Ins（1，3，4，5）P4的初始蓄积速率与卡巴胆碱观察到的相似，但这些肌醇磷酸盐的量在加入组胺后5分钟内恢复到对照值。结果表明，尽管毒蕈碱受体和H1-组胺受体刺激对磷酸肌醇水解的急性效应非常相似，但组胺受体迅速脱敏，而毒蕈碱受体则不然。这种对组胺受体功能的影响显然是同源的，因为用组胺预孵育1321 N1细胞并没有降低随后对卡巴胆碱的反应。
Although activation of muscarinic cholinergic receptors on 1321N1 human astrocytoma cells results in a linear accumulation of inositol phosphates for up to 60 min in the presence of LiCl [Masters, Quinn & Brown (1985) Mol. Pharmacol. 27, 325-332], activation of H1-histamine receptors resulted in an increase in total inositol phosphate formation that was maintained for less than 5 min. The effects of stimulation of these two receptors on accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] were also examined. Incubation of 1321N1 cells with carbachol resulted in a rapid accumulation of all three inositol phosphates, reaching a maximum within 30 s; this elevated value was maintained for up to 60 min. The rate of disappearance of Ins(1,3,4)P3 from carbachol-treated cells after the addition of atropine paralleled or exceeded the rate of disappearance of Ins(1,4,5)P3. Although the initial rates of accumulation of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1,3,4,5)P4 in the presence of histamine were similar to that observed with carbachol, the amounts of these inositol phosphates had returned to control values within 5 min after the addition of histamine. The results indicate that, although the acute effects of muscarinic receptor and H1-histamine receptor stimulation on phosphoinositide hydrolysis are very similar, the histamine receptor is desensitized rapidly, whereas the muscarinic receptor is not. This effect on histamine-receptor function is apparently homologous, since preincubation of 1321N1 cells with histamine did not decrease the subsequent response to carbachol.