H3 receptor-mediated inhibition of noradrenaline release: an investigation into the involvement of Ca2+ and K+ ions, G protein and adenylate cyclase

Abstract

The present study was aimed at the identification of mechanisms following the activation of histamine H3 receptors. Mouse brain cortex slices preincubated with 3H-noradrenaline were superfused and the (H3 receptor-mediated) effect of histamine on the electrically evoked tritium overflow was studied under a variety of conditions. The extent of inhibition produced by histamine was inversely related to the frequency of stimulation used to evoke tritium overflow and to the Ca2+ concentration in the superfusion medium. An activator (levcromakalim) and blocker (glibenclamide) of ATP-dependent K+ channels did not affect the electrically evoked tritium overflow and its inhibition by histamine. A blocker of voltage-sensitive K+ channels, tetraethylammonium (TEA), increased the evoked overflow and attenuated the inhibitory effect of histamine. TEA also reduced the inhibitory effect of noradrenaline and prostaglandin E2 on the evoked overflow. When the facilitatory effect of TEA on the evoked overflow was compensated for by reducing the Ca2+ concentration in the superfusion medium, TEA did no longer attenuate the effect of histamine. Exposure of the slices to the SH group-alkylating agent N-ethylmaleimide increased the evoked overflow and attenuated the inhibitory effect of histamine; both effects were counteracted by the SH group-protecting agent dithiothreitol, which, by itself, did not affect the evoked overflow and its inhibition by histamine. Mouse brain cortex membranes were used to study the effect of the H3 receptor agonist R-(-)-alpha-methylhistamine on the basal cAMP accumulation and on the accumulation stimulated by forskolin or noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus

“…a larger depression was observed at lower external calcium concentrations. A similar relationship has previously been demonstrated for H× receptor-mediated depression of histamine (Arrang et al 1985) and noradrenaline release (Schlicker et al 1994). Such a relationship is consistent with an effect of histamine on calcium influx (i.e.…”

“…Thus, we conclude that it is more likely that histamine inhibits several types of presynaptic calcium channels rather than activating presynaptic potassium channels. Studies on the histamine H×-mediated inhibition of cortical noradrenaline release also concluded that potassium channels were not responsible for the effect (Schlicker et al 1994). Blockers or activators of ATP-sensitive potassium channels did not affect the histaminergic inhibition.…”

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…This autoinhibition by H 3 receptor agonists [e.g., (R)-a-methylhistamine; 33] and its removal by H 3 receptor antagonists/partial agonists can be demonstrated in recordings from TMN neurons. As presynaptic heteroreceptors, H 3 receptors control the release of several other transmitters, including biogenic amines (Schlicker et al, 1994(Schlicker et al, , 1999, acetylcholine (Blandina et al, 1996;Arrang, 2007), GABA (Jang et al, 2001), and glutamate; field potentials evoked by stimulation of glutamate fiber bundles, e.g., in hippocampus or striatum, show a marked decrease in the presence of an H 3 receptor agonist (Brown and Haas, 1999;Doreulee et al, 2001) (Fig. 12).…”

L-histidine enhances learning in stressed zebrafish

“…Besides being histaminergic auto-receptors, H 3 receptors also function as presynaptic heteroreceptors controlling the release of serotonin (31), acetylcholine (32) and several other neurotransmitters (33,34). It has been shown that histaminergic H 3 antagonists (ciproxifan, clobenpropit and thioperamide), directly administered to the basolateral amygdala, decreased spontaneous acetylcholine release.…”