Homologous desensitization of substance-P-induced inositol polyphosphate formation in rat parotid acinar cells.
Homologous desensitization of substance-P-induced inositol polyphosphate formation in rat parotid acinar cells.
复制标题
大鼠腮腺腺泡细胞中 P 物质诱导的肌醇多磷酸形成的同源脱敏。
DOI：
10.1042/bj2440647
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
PutneyJr,JW
中科院分区：
文献类型：
--
作者：
Sugiya,H;Tennes,KA;PutneyJr,JW
最大浓度的P物质和乙酰甲胆碱诱导[3H]肌醇三磷酸（[3H]IP3）的形成迅速增加。约1分钟后，P物质处理的细胞中的[3H]IP3停止进一步增加，而乙酰甲胆碱处理的细胞中的[3H]IP3继续增加。向P物质处理的细胞中加入乙酰甲胆碱导致[3H]IP3迅速增加，而第二次加入10倍过量的P物质则没有影响。用物质P预处理细胞，然后通过洗涤除去物质P，导致对物质P的第二次应用的反应降低。涉及用乙酰甲胆碱预处理的类似方案对随后对物质P的反应没有影响。[3H] P物质与物质P处理的细胞结合的分析表明，P物质的受体数目减少，但受体对P物质的亲和力不受影响。P物质预处理后，长时间孵育（2小时）恢复了细胞对P物质的反应，测量为[3H]IP3的形成，并将结合位点的数量恢复到对照值。这些研究结果表明，在大鼠腮腺，P物质诱导其受体的同源脱敏，这涉及到一个缓慢可逆的下调或隔离的P物质结合位点。
Maximal concentrations of substance P and methacholine induced a rapid increase in [3H]inositol trisphosphate ([3H]IP3) formation. After about 1 min, the [3H]IP3 in the substance-P-treated cells ceased to increase further, whereas in the methacholine-treated cells [3H]IP3 continued to increase. Addition of methacholine to the substance-P-treated cells caused a rapid increase in [3H]IP3, whereas a second addition of a 10-fold excess of substance P had no effect. Pretreatment of cells with substance P, followed by removal of the substance P by washing, resulted in a decreased response to a second application of substance P. A similar protocol involving pretreatment with methacholine had no effect on subsequent responsiveness to substance P. Analysis of [3H]substance P binding to substance-P-treated cells indicated that the number of receptors for substance P was decreased, but the affinity of the receptors for substance P was unaffected. After substance P pretreatment, a prolonged incubation (2 h) restored responsiveness of the cells to substance P, measured as [3H]IP3 formation, and restored the number of binding sites to control values. These findings indicate that, in the rat parotid gland, substance P induces a homologous desensitization of its receptor, which involves a slowly reversible down-regulation or sequestration of substance-P-binding sites.