We have studied the effect of histamine H 3 receptor (H 3R) activation on the depolarization-evoked release of labeled neurotransmitters from slices of the rat olfactory bulb (rOB). The presence of pre-synaptic H 3Rs was evidenced by the specific binding of the H 3R ligand N-α-[methyl- 3H]histamine to membranes from rOB synaptosomes (maximum binding, B max, 106 ± 19 fmol/mg protein; dissociation constant, K d, 0.68 ± 0.11 nM) which was inhibited by selective H 3R ligands (immepip, (R)(-)-α- methylhistamine (RAMH) and clobenpropit) with affinities similar to those previously reported for H 3Rs expressed in other rat brain areas. Perfusion of rOB slices with the selective H 3R agonist RAMH (0.1 and 1 μM) had no effect on the release of [ 3H]-γ-aminobutyric acid ([ 3H]-GABA), [ 3H]-d-aspartate, [ 3H]- dopamine or [ 3H]-5-hydroxytryptamine ([ 3H]-5-HT) evoked by depolarization with high K + (20 or 40 mM). [ 3H]- Noradrenaline release induced by 20 mM K + was reduced in a modest but significant manner by RAMH (94.9 ± 1.7% and 83.1 ± 2.1% of control release at 0.1 and 1 μM, respectively). The effect of 1 μM RAMH was blocked by the selective H 3R antagonist/inverse agonist clobenpropit (5 μM). When tested alone clobenpropit and a second H 3R antagonist/inverse agonist, ciproxifan (both at 1 μM) significantly increased K +-evoked [ 3H]-noradrenaline release to 119.4 ± 4.2% and 120.0 ± 3.7% of K + alone, respectively. Ciproxifan (1 μM) had no effect on the depolarization-evoked release of the other labeled neurotransmitters. These data indicate that H 3Rs with constitutive activity modulate noradrenaline release in rOB, presumably through a pre-synaptic action. © 2011 Elsevier Ltd. All rights reserved.
- H receptor 3
- Noradrenaline release
- Olfactory bulb
- Pre-synaptic receptors
Aquino-Miranda, G., Osorio-Espinoza, A., Escamilla-Sánchez, J., González-Pantoja, R., Ortiz, J., & Arias-Montaño, J. A. (2012). Histamine H <inf>3</inf> receptors modulate depolarization-evoked [ <sup>3</sup>H]-noradrenaline release from rat olfactory bulb slices. Neuropharmacology, 62, 1127-1133. https://doi.org/10.1016/j.neuropharm.2011.11.004