Histamine H3 receptors modulate depolarization-evoked [3H]-noradrenaline release from rat olfactory bulb slices

We have studied the effect of histamine H-3 receptor (H3R) activation on the depolarization-evoked release of labeled neurotransmitters from slices of the rat olfactory bulb (rOB). The presence of presynaptic H(3)Rs was evidenced by the specific binding of the H3R ligand N-alpha-[methyl-H-3]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 H3R ligands (immepip, (R)(-)-alpha-methylhistamine (RAMH) and clobenpropit) with affinities similar to those previously reported for H(3)Rs expressed in other rat brain areas. Perfusion of rOB slices with the selective H3R agonist RAMH (0.1 and 1 mu M) had no effect on the release of [H-3]-gamma-aminobutyric acid ([H-3]-GABA), [H-3]-D-aspartate, [H-3]-dopamine or [H-3]-5-hydroxytryptamine ([H-3]-5-HT) evoked by depolarization with high K+ (20 or 40 mM). [H-3]-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 mu M, respectively). The effect of 1 mu M RAMH was blocked by the selective H3R antagonist/inverse agonist clobenpropit (5 mu M). When tested alone clobenpropit and a second H3R antagonist/inverse agonist, ciproxifan (both at 1 mu M) significantly increased K+-evoked [H-3]-noradrenaline release to 119.4 +/- 4.2% and 120.0 +/- 3.7% of K+ alone, respectively. Ciproxifan (1 mu M) had no effect on the depolarization-evoked release of the other labeled neurotransmitters. These data indicate that H(3)Rs with constitutive activity modulate noradrenaline release in rOB, presumably through a pre-synaptic action. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. (C) 2011 Elsevier Ltd. All rights reserved.