Magnetic field desensitizes 5-HT1B receptor in brain:: pharmacological and functional studies

It was previously suggested that exposure to magnetic fields (MFs) could generate dysfunction of the CNS. The physiological manifestations described lead us to postulate that these symptoms might be related to a dysfunction of the serotonergic system and particularly of the 5-HT1B receptors. Accordingly, MFs could modify the conformation of these receptors altering their functional activities. In rat brain membrane preparations, we showed that the affinity constant of 5-HT for 5-HT1B receptors was modified under exposure to MFs since K-d varied from 4.7 +/- 0.5 to 12 +/- 3 nhl in control and exposed (2.5 mT) membranes, respectively. This effect was intensity-dependent (the sigmoidal dose-response curve was characterized by an EI50 of 662 +/- 69 mu T and a maximal increase of 321 +/- 13% of the control K-d), reversible, temperature-dependent and specific to the 5-HT1B receptors. Similar results have also been obtained with the human 5-HT1B receptors. In parallel assays, the functional activity of 5-HT1B receptors was investigated. The capacity of a 5-HT1B agonist to inhibit the cAMP production was reduced by 37% (53.7 +/- 3.5% to 33.7 +/- 4.1%) following exposure to MFs and the cellular activity of the receptors (inhibition of the synaptosomal release of 5-HT) also was markedly reduced (66.5 +/- 3.2% to 28.5 +/- 4.2%). These results clearly show that in in vitro assays, MF specifically interacts with 5-HT1B receptors, inducing structural changes of the protein that result in a functional desensitization of the receptors. Thus, in vivo, exposure to MFs may lead to physiological changes, particularly in the field of mood disorders where the 5-HT system is strongly involved. (C) 2000 Elsevier Science B.V. All rights reserved.