text: Serotonin transporter production and degradation rates: studies with RTI-76.
  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 (-1)h(-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.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: SERT SERT SERT SERT SERT serotonin transporter SERT SERT SERT SERT [3H]-5-HT Serotonin transporter RTI-76 RTI-76 Citalopram RTI-76 serotonin RTI-76 Serotonin RTI-76