Pre-synaptic histamine H3 receptors regulate glutamate, but not GABA release in rat thalamus.
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.
Garduño-Torres
Belén
B
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav), Apdo. postal 14-740, 07000 México, D.F., Mexico.
Treviño
Mario
M
Gutiérrez
Rafael
R
Arias-Montaño
José-Antonio
JA
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*
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