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Communication Dans Un Congrès Année : 2006

Effects of ELF and static magnetic fields on the 5-HT1B serotonin receptor

Résumé

Ob jective. Massot et al. (2000, Brain Res 858, 143-150) have shown that exposure to 50 Hz magnetic fields (MF) caused a reversible decrease of the affinity of the 5-HT1B serotoninergic GPCR receptor in both rat brain membranes and cells transfected with the human 5-HT1B receptor at field strengths above 0.6 mT. Using [3H]5-HT, we have attempted to confirm these findings and assess the role of both induced currents and static magnetic fields in the elicitation of the effect. Modeling was then performed to determine the potential site of the action of the magnetic field. Methods. Adult male Wistar rats were used to obtain the brain cell membranes. The membrane preparation and the binding assay have already been described by Massot et al. (2000). The main exposure system was composed of two identical sets of Merritt coils. The 96-well plates containing the rat brain membranes were placed in temperature-regulated containers located inside each set of coils, which could be independently activated. Samples were either exposed or sham-exposed in a randomized and blind fashion. This setup was also activated using two other generators to provide a static or a sine-wave MF at 400 Hz. Temperature and MF strength in each container were monitored in real time. Exposures lasted for 1 hour and were carried out at 25◦ C . Results. We have successfully replicated the results of Massot et al. (Espinosa et al. 2006, Bioelectromagnetics, in press), by showing that (i) a similar decrease in binding affinity occurs (3-fold increase in Kd) under exposure to MF at 50 Hz 1 mT, (ii) other subtypes of 5-HT receptors were not affected by the exposure, (iii) induced currents were not involved in the effect. We also showed that static MF had a different effect from the 50 Hz field and that the polarity of the field was a critical factor in the elicitation of the effect. One more recent finding was the absence of effect of MF exposure in the presence of another agonist of the 5-HT1B receptor, namely 5-CT (5-carboxyamidotryptamine), which is more specific that 5-HT, albeit with a very similar chemical structure. We have also shown that it is unlikely that the effect of the MF is on the fluidity of the membrane surrounding the receptor. Modeling of the kinetics using the extended ternary model based on the agonist (5-HT)-receptor-G protein system showed that some useful information could be gained on the site of action of the MF field (described in above reference). Discussion. Overall, this set of results on the binding of the 5-HT receptor under exposure to 50 Hz 1 mT field constitutes one of the few replicated observations of an effect of ELF MF in the mT range. Moreover, the fact that only one type of receptors among the several studied is affected by exposure shows that the mechanism for such action is highly specific. There is little information available on such effects of MF exposure on the functioning of GPCRs. Conclusion. Based on the experimental and modeling data described above, our plan is thus to (i) model further the kinetics of the system to extract as much information as possi- ble from the available experimental data, (ii) do molecular modeling of the agonist-receptor complex to determine how the exposure could affect the docking of the G protein, and (iii) design and perform an experiment based on a ion-channel GPCR so that real-time mea- surements of ion currents under real or sham exposure can bring further information about the mechanism of the effect. Update on results originating from these three approaches will be presented at the meeting
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Dates et versions

hal-00161738 , version 1 (11-07-2007)

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  • HAL Id : hal-00161738 , version 1

Citer

B. Veyret, J. Espinosa, M. Liberti, G. Ruffié, I. Lagroye. Effects of ELF and static magnetic fields on the 5-HT1B serotonin receptor. 28th Annual Meeting of the BEMS, Jun 2006, Cancun, Mexico. ⟨hal-00161738⟩
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