Serotonin transporter production and degradation rates: studies with RTI-76.
Serotonin transporter production and degradation rates: studies with RTI-76.
复制标题
血清素转运蛋白的产生和降解率：使用 RTI-76 进行的研究。
DOI：
10.1016/s0006-8993(99)01761-8
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发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Kuhar,MJ
中科院分区：
文献类型：
--
作者：
Vicentic,A;Battaglia,G;Carroll,FI;Kuhar,MJ
本研究的目的是通过测定血清素转运体（SERT）的产生速率(r)、降解速率常数(k)和恢复半衰期（t1/2）来检测其周转率。SERT的周转是通过给予RTI-76（一种不可逆的配体结合抑制剂）后的结合恢复率来确定的。在初步研究中，RTI-76在大鼠大脑皮层的体外培养产生了对SERT结合密度（Bmax）的水洗和耐温抑制。西酞普兰对rti -76诱导的SERT结合抑制具有保护作用。在脑室内注射100 nmol RTI-76 6小时后，海马和纹状体中SERT结合的剂量和时间依赖性降低（- 60%），而Kd没有变化。SERT结合密度在几天后恢复，在第14天达到控制水平。回收率曲线符合蛋白质合成和降解的标准模型。在海马和纹状体中分别测定SERT的转换参数，这两个区域分别接受来自中脑背核和中脑正中核的血清素能神经支配。海马区蛋白质生成速率常数为2.36 fmol mg - 1h−1；降解速率常数为0.0077 h−1；SERT恢复的半衰期为3.4天。纹状体的数值相似。[3H]-5-HT摄取的减少和恢复与SERT结合的恢复高度相关（r=0.93）。
The objective of this study was to examine the turnover of the serotonin transporter (SERT) by determining its production rate (r), degradation rate constant (k) and half-life of recovery (t1/2). The turnover of SERT was determined from the rate of recovery of binding after administration of RTI-76, an irreversible inhibitor of ligand binding. In preliminary studies, in vitro incubation of rat cerebral cortex with RTI-76 produced a wash and temperature resistant inhibition of SERT binding densities (Bmax). Citalopram protected against the RTI-76-induced inhibition of SERT binding. Following 6 h of in vivo intracerebroventricular injections of 100 nmol of RTI-76, there was a dose- and time-dependent reduction (−60%) of SERT binding in hippocampus and striatum, without a change in the Kd. SERT binding densities recovered over several days, reaching control levels by day 14. The recovery curve fit the standard model of protein synthesis and degradation. The turnover parameters of SERT were determined in hippocampus and striatum, regions that receive serotonergic innervation from the dorsal and median midbrain raphe nuclei, respectively. In the hippocampus, the production rate constant was 2.36 fmol mg protein−1h−1; the degradation rate constant was 0.0077 h−1; and the half-life of the SERT recovery was 3.4 days. The values in the striatum were similar. The decrease and recovery of [3H ]-5-HT uptake correlated highly (r=0.93) with the recovery of SERT binding.