title: Magnetic field desensitizes 5-HT(1B) receptor in brain: pharmacological and functional studies.
abstract: 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-HT(1B) 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-HT(1B) receptors was modified under exposure to MFs since K(d) varied from 4.7+/-0.5 to 12+/-3 nM in control and exposed (2.5 mT) membranes, respectively. This effect was intensity-dependent (the sigmoidal dose-response curve was characterized by an EI(50) of 662+/-69 microT and a maximal increase of 321+/-13% of the control K(d)), reversible, temperature-dependent and specific to the 5-HT(1B) receptors. Similar results have also been obtained with the human 5-HT(1B) receptors. In parallel assays, the functional activity of 5-HT(1B) receptors was investigated. The capacity of a 5-HT(1B) 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-HT(1B) 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.
authors.affiliation: Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, 25-28 rue du docteur Roux, Paris, France. omassot@pasteur.fr
authors.forename: O
authors.initials: O
authors.lastname: Massot
authors.forename: B
authors.initials: B
authors.lastname: Grimaldi
authors.forename: J M
authors.initials: JM
authors.lastname: Bailly
authors.forename: M
authors.initials: M
authors.lastname: Kochanek
authors.forename: F
authors.initials: F
authors.lastname: Deschamps
authors.forename: J
authors.initials: J
authors.lastname: Lambrozo
authors.forename: G
authors.initials: G
authors.lastname: Fillion
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000528:radiation effects; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism / Q000528:radiation effects; D002540:Cerebral Cortex / Q000378:metabolism / Q000528:radiation effects*; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004574:Electromagnetic Fields / Q000009:adverse effects*; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D011487:Protein Conformation / Q000187:drug effects / Q000528:radiation effects; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013696:Temperature; D014162:Transfection
chemical_list: C470302:HTR1B protein, human; D008024:Ligands; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D005576:Colforsin; D012701:Serotonin; D006160:Guanosine Triphosphate; D000242:Cyclic AMP