Magnetic field desensitizes 5-HT(1B) 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-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.
Massot
O
O
Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, 25-28 rue du docteur Roux, Paris, France. omassot@pasteur.fr
Grimaldi
B
B
Bailly
J M
JM
Kochanek
M
M
Deschamps
F
F
Lambrozo
J
J
Fillion
G
G
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
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