H2 receptor-mediated facilitation and H3 receptor-mediated inhibition of noradrenaline release in the guinea-pig brain

Abstract

The effect of histamine and related drugs on the tritium overflow evoked electrically (0.3 Hz) or by introduction of Ca2+ ions into Ca2+-free K+-rich (25 mmol/l) medium containing tetrodotoxin was studied in superfused guinea-pig brain cortex, cerebellum, hippocampus or hypothalamus slices and in mouse brain cortex slices preincubated with 3H-noradrenaline. The electrically evoked tritium overflow in guinea-pig cortex slices was inhibited by histamine; the H3 receptor antagonist clobenpropit reversed the effect of histamine to a slight facilitation. The facilitatory effect of histamine (obtained in the presence of clobenpropit) was not affected by the H1 receptor antagonist mepyramine but abolished by the H2 receptor antagonist ranitidine. In the absence of clobenpropit, ranitidine augmented the inhibitory effect of histamine. In slices superfused in the presence of ranitidine, the evoked overflow was inhibited by histamine and, more potently, by the H3 receptor agonist R-alpha-methylhistamine in a concentration-dependent manner (maximum inhibitory effect obtained for both agonists 30-35%). The concentration-response curve of histamine was shifted to the right by the H3 receptor antagonist thioperamide. R-alpha-methylhistamine inhibited the electrically evoked tritium overflow also in guinea-pig cerebellar, hippocampal and hypothalamic slices. In cortex slices superfused in the presence of clobenpropit, the H2 receptor agonists impromidine and, less potently, R-sopromidine facilitated the evoked overflow in a concentration-dependent manner. S-Sopromidine only tended to increase the evoked overflow. The effect of impromidine was counteracted by the H2 receptor antagonists ranitidine and cimetidine. The extent of the maximum facilitatory effect of impromidine (by 15-20%) was about the same when (i) the Ca2+ concentration in the medium was reduced from 1.3 to 0.98 mmol/l, (ii) the time of exposure to impromidine was reduced from 28 to 8 min or (iii) cerebellar, hippocampal or hypothalamic slices were used instead of cortical slices. The Ca2+-induced tritium overflow in guinea-pig cortex slices was inhibited by histamine (in the presence of ranitidine); this effect was abolished by clobenpropit. In slices superfused in the presence of clobenpropit, impromidine failed to facilitate the Ca2+-evoked tritium overflow. The electrically evoked tritium overflow in mouse brain cortex slices was inhibited by histamine by about 60% (both in the absence or presence of ranitidine). The inhibitory effect of histamine was abolished (but not reversed) by clobenpropit. In conclusion, noradrenaline release in the guinea-pig brain cortex is inhibited via presynaptic H3 receptors and facilitated via H2 receptors not located presynaptically. In the mouse brain cortex, only inhibitory H3 receptors occur. The extent of the H3 receptor-mediated effect is more marked in the mouse than in the guinea-pig brain cortex.

Nociceptin inhibits noradrenaline release in the mouse brain cortex via presynaptic ORL1 receptors

“…The experiments of our study were performed on superfused mouse, rat and guinea-pig brain cortex slices preincubated with [ 3 H]noradrenaline, in which the electrically evoked tritium overflow is virtually abolished by tetrodotoxin or omission of Ca 2+ ions, suggesting that it represents quasi-physiological noradrenaline release (Taube et al 1977;Schlicker et al 1992;Timm et al 1998). Desipramine and rauwolscine were routinely added to the superfusion medium in order to block the neuronal noradrenaline transporter and the α 2 -autoreceptor on the noradrenergic neurones, respectively.…”

Modulation of dopamine release in the guinea‐pig retina by Gi‐ but not by Gs‐ or Gq‐protein‐coupled receptors

“…In some experiments, tetrodotoxin 1 μ M was added or Ca 2+ ions were omitted from 82 min of superfusion onward. Tetrodotoxin or omission of Ca 2+ ions virtually abolished the electrically‐evoked tritium overflow in retinal discs and in slices from the hippocampus, hypothalamus, striatum (n ≥ 4, results not shown) and cerebral cortex [13].…”

Neuropharmacology of Histamine in Brain

“…H 2 receptors that are not presynaptically located facilitate noradrenaline release from superfused guinea pig brain slices [244]. In vivo, activation of H 2 receptors enhances the release of acetylcholine in the ventral striatum [179], the medial septumdiagonal band complex [245], and the hippocampus [246,247].…”

“…However, the inhibition of dopamine neuron activity by H 3 heteroreceptors may become operating after methamphetamine administration, which is known to increase histamine release [302,303], as shown by the potentiation of methamphetamineinduced accumbal dopamine release induced by H 3 receptor antagonists/inverse agonists [304]. H 3 heteroreceptors inhibit in vitro noradrenaline release in the brain from various species, including human [244,305,306], but play also a minor role on noradrenaline turnover [299][300][301] and release in vivo [307]. H 3 heteroreceptors also inhibit serotonin release in the cortex [308] and substantia nigra [309] but do not affect serotonergic transmission under basal conditions in vivo [310].…”