title: Pre-synaptic histamine H3 receptors regulate glutamate, but not GABA release in rat thalamus.
abstract: We have investigated the presence of histamine H(3) receptors (H(3)Rs) on rat thalamic isolated nerve terminals (synaptosomes) and the effect of their activation on glutamate and GABA release. N-alpha-[methyl-(3)H]histamine ([(3)H]-NMHA) bound specifically to synaptosomal membranes with dissociation constant (K(d)) 0.78+/-0.20 nM and maximum binding (B(max)) 141+/-12fmol/mg protein. Inhibition of [(3)H]-NMHA binding by histamine and the H(3)R agonist immepip fit better to a two-site model, whereas for the H(3)R antagonist clobenpropit the best fit was to the one-site model. GTPgammaS (30 microM) decreased [(3)H]-NMHA binding by 55+/-4% and made the histamine inhibition fit better to the one-site model. Immepip (30 nM) induced a modest, but significant increase (113+/-2% of basal) in [(35)S]-GTPgammaS binding to synaptosomal membranes, an effect prevented by clobenpropit (1 microM) and by pre-treatment with pertussis toxin. In thalamus synaptosomes depolarisation-induced, Ca(2+)-dependent glutamate release was inhibited by histamine (1 microM, 25+/-4% inhibition) and immepip (30 nM, 38+/-5% reduction). These effects were reversed by clobenpropit (1microM). Conversely, immepip (up to 1 microM) had no effect on depolarisation-evoked [(3)H]-GABA release. Extracellular synaptic responses were recorded in the thalamus ventrobasal complex by stimulating corticothalamic afferents. H(3)R activation reduced by 38+/-7% the glutamate receptor-mediated field potentials (FPs), but increased the FP2/FP1 ratio (from 0.86+/-0.03 to 1.38+/-0.05) in a paired-pulse paradigm. Taken together, our results confirm the presence of H(3)Rs on thalamic nerve terminals and show that their activation modulates pre-synaptically glutamatergic, but not GABAergic neurotransmission.
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav), Apdo. postal 14-740, 07000 México, D.F., Mexico.
authors.forename: Belén
authors.initials: B
authors.lastname: Garduño-Torres
authors.forename: Mario
authors.initials: M
authors.lastname: Treviño
authors.forename: Rafael
authors.initials: R
authors.lastname: Gutiérrez
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Arias-Montaño
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005071:Evoked Potentials / Q000187:drug effects / Q000528:radiation effects; D018698:Glutamic Acid / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000493:pharmacokinetics; D037342:Pertussis Toxin / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism* / Q000648:ultrastructure; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D006633:Histamine Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D018100:Receptors, Histamine H3; D014316:Tritium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D015761:4-Aminopyridine; D037342:Pertussis Toxin; D013890:Thiourea; C086108:clobenpropit