Histamine H3 receptor, activation

Blandina P, Giorgetti M, Bartolini L, Cecchi M, Timmerman H, et al. 1996. Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats. Br J Pharmacol 119(8) 1656-1664. 

Contrastingly, it was found that presynaptic histamine H3-receptor activation lowers the hypertensive effect evoked by nicotinic stimulation of sympathetic ganglia (Oudart et al., 1995), or by electrical stimulation of the spinal sympathetic nerves (Malinowska and Schlicker, 1991, Godlewski et al., 1997a). In spontaneously hypertensive rats, these receptors are probably activated by endogenous histamine, since thioperamide increases arterial pressure. Therefore, histamine H3-receptors appear to be operative in hypertension, where histamine could play a modulatory role in the control of sympathetic system hyperreactivity (Godlewski et al., 1997a). 

Similarly to what identified in the rat, histamine H3 receptor activation does not contribute to prostacyclin production in coltured human endothelial cells (Bull et al., 1992). There are no findings explaining any possible involvement of these receptors in the control of endothelial functions in humans. 

Oike, M., Kitamura, K., Kuriyama, H., 1992. Histamine H3-receptor activation augments voltage-dependent Ca2+ current via GTP hydrolysis in rabbit saphenous artery. J. Physiol. 448, 133-152. 

Garcia, M., Floran, B., Arias-Montano, J.A., Young, J.M. and Aceves, J. (1997). Histamine H3-receptor activation selectively inhibits dopamine Di-dependent [3H]-Y-aminobutyric acid release from depolarisation-stimulated slices of rat substantia nigra pars reticulata. Neuroscience, in press. 

Table 3 Tissues in which neurotransmitter release is decreased by presynaptic histamine H3 receptor activation...

Imamura M, Lander HM, Levi R Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine Aj-receptors and a2-adrenoceptors. Circ Res 1996 78 475. 

The key to an understanding of the biology of the histamine H3 receptor is the fact that it is an inhibitory auto- and heteroreceptor. Activation of the H3... 

McLeod, R. L., Aslanian, R., del Prado, M. et at (1998). Sch 50971, an orally active histamine H3 receptor agonist, inhibits central neurogenic vascular inflammation and produces sedation in the guinea pig. J. Pharmacol. Exp. Ther. 287, 43-50. 

Wieland, K., Bongers, G., Yamamoto, Y. etal. Constitutive activity of histamine H3 receptors stably expressed in SK-N-MC cells display of agonism and inverse agonism by H3 antagonists. /. Pharmacol. Exp. Ther. 299 908-914, 2001. 

Cannon, K. E., Nalwalk, J. W., Stadel, R. etal. Activation of spinal histamine H3 receptors inhibits mechanical nociception. Eur. J. Pharmacol. 470 139-147, 2003. 

The biological effects of histamine (Table 15.1) are mediated via three receptor subtypes, HI, H2 and H3 that are linked to G protein but activate different cell-signalling systems. The histamine HI receptor is associated with the phospholipase C-catalysed formation of inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DAG). The H2-receptor is coupled to adenylyl cyclase, increasing the production of cAMP. The cellular messenger system involved in H3-receptor activation has not been fully defined, but it may couple to N-type Ca2+-channels. The genes encoding for HI and H2 receptors have been cloned. A mutation of the human H2 receptor has been linked to schizophrenia. 

Arrang J-M, Morisset S, Gbahou F Constitutive activity of the histamine H3 receptor. Trends Pharmacol Sci 2007 28 350. [PMID 17573125] Barnes PJ Histamine and serotonin. Pulm Pharmacol Ther 2001 14 329. [PMID 11603947]... 

Imamura M, Poli E, Omoniyi AT, Levi R (1994) Unmasking of activated histamine H3-receptors in myocardial ischemia their role as regulators of exocytotic norepinephrine release. J Pharmacol Exp Ther 271 1259-1266. 

High densities of H3 receptors were found in ACh-rich areas such as the cerebral cortex [40]. Furthermore, two different laboratories reported that H3 receptors are involved in the inhibitory effects of histamine on potassium-evoked release of [3H]-acetylcholine (ACh) [53, 54]. However, H3 receptor activation failed to inhibit [3H]-ACh release from rat cortical synaptosomes [54]. Since, as noted above, prudence must always be exerted in in-vivo extrapolation of in-vitro observations, we investigated the effect of histamine on the release of ACh from the cortex of freely moving rats and characterized the underlying mechanisms [55-58]. 

Figure 3. Effect of N -methylhistamine produced by Helicobacter pylori on acid secretion On the one hand, this compound may reduce acid secretion by inhibiting, via H3 receptor activation, histamine synthesis and release from ECL cells on the other hand, FI3 receptor activation on D cells, with consequent inhibition of somatostatin release, may increase acid secretion. Additionally, direct activation of H2 receptors on parietal cell by N -metylhistamine must also be considered (this mechanism is not shown in the scheme).

Activities of some histamine H3 receptor antagonists on various in vitro functional models of the guinea pig intestine... 

Early evidence that prejunctional histamine H3-receptors may modulate the sympathetic nerve activity on the heart was provided by Luo et al., (1991). These authors clearly stated that the selective H3-agonist (R)a-methylhistamine attenuates the inotropic response induced by transmural stimulation of the adrenergic nerve terminals in the isolated right atrium, without affecting basal contractile force of the preparation or the positive inotropic effect elicited by exogenous noradrenaline. The effect of (R)a-methylhistamine, which is not modified by Hi and H2-receptor blockade, was reversed by the specific H3-receptor antagonist thioperamide, at concentrations which do not influence the inhibitory activity mediated by other presynaptic receptors, like a2-adrenoceptors. 

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