Presynaptic H3 receptors

Histamine produces its pharmacological actions by three subtypes of receptors the postsynaptic Hi and H2 receptors and the presynaptic H3 receptor. The H3 receptor is mainly located in the central nervous system (CNS), where it acts as an inhibitory autoreceptor in the central histaminergic neuronal pathways [176]. A number of therapeutic applications have been proposed for selective H3 receptor antagonists, including several CNS disorders such as Alzheimer s disease. Attention Deficit Hyperactivity Disorder, Schizophrenia, or for enhancing memory or obesity control. 

Arrang, J. M., Garbarg, M. Schwartz, J. C. (1987b). Autoinhibition of histamine synthesis mediated by presynaptic H3-receptors. Neuroscience 23, 149-57. 

Schlicker, E., Fink, K., Hinterthaner, M. 8r Gothert, M. (1989). Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors. Naunyn Schmiedehergs Arch. Pharmacol. 340, 633-8. 

Endogenous histamine has a modulating role in a variety of inflammatory and immune responses. Upon injury to a tissue, released histamine causes local vasodilation and leakage of plasma-containing mediators of acute inflammation (complement, C-reactive protein) and antibodies. Histamine has an active chemotactic attraction for inflammatory cells (neutrophils, eosinophils, basophils, monocytes, and lymphocytes). Histamine inhibits the release of lysosome contents and several T- and B-lymphocyte functions. Most of these actions are mediated by H2 or H4 receptors. Release of peptides from nerves in response to inflammation is also probably modulated by histamine, in this case acting through presynaptic H3 receptors. 

Schlicker E, Fink K, Detzner M, Gothert M (1993) Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors. J Neural Transm [Gen Sect] 93 1-10. 

Fink K, Schlicker E, Neise A, Gothert M (1990) Involvement of presynaptic H3 receptors in the inhibitory effect of histamine on serotonin release in the rat brain cortex. Naunyn-Schmiedeberg s Arch Pharmacol 342 513-519. 

Fink K, Schlicker E, Gothert M (1994) N-Methyl-D-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H3-receptors. Naunyn-Schmiedeberg s Arch Pharmacol 349 113-117. 

In summary, the present findings indicate that activation of presynaptic H3 receptors inhibits AVP secretion induced by hyperosmolality - an effect which is similar to and in accordance with that of blockade of HA synthesis or postsynaptic H1 and H2 receptors. 

Much like what was described in heart and lung, neuropeptides may release histamine from mast cells, which in turn may act on presynaptic H3-receptors (Matsubara et al., 1992). In this regard, endogenous histamine exerts a two faceted influence on neurogenic inflammation, since this substance may also cause vasodilatation and rise in vascular permeability through the Hi-receptor/NO-pathway (Levi et al., 1991 Lassen et al., 1995). 

Malinowska, B., Schlicker, E., 1993b. Identification of endothelial Hi, vascular H2 and cardiac presynaptic H3 receptors in the pithed rat. Naunyn-Schmiedeberg s Arch Pharmacol. 347, 55-60. 

Wang, Y.Z., Cooke, H.J., 1990. Presynaptic H3 receptors regulate cyclical Cl secretion in guinea pig distal colon. Gastroenterology 98 (Suppl), A400. 

Presynaptic histamine receptors are more uniform than presynaptic dopamine receptors. Only one type, H3, has been identified with certainty. Like presynaptic dopamine receptors, presynaptic H3 receptors occur as auto- and heteroreceptors... 

Table 3). They have been detected both functionally (Table 3) and, morphologically, by comparison of the distribution of H3 receptor mRNA and H3 receptor protein. By the latter approach it has been shown, for example, that thalamo-cortical and hippocampal pyramidal glutamate neurons and striato-nigral as well as striato-pallidal GABA neurons possess presynaptic H3 receptors (see Pillot et al. 2002 Jin and Panula 2005 see also immunohistochemical detection in Section 3.9). 

Presynaptic H3 receptors also are uniform in their signal transduction. They couple to Gi/o proteins and decrease the depolarization-induced release of neurotransmitters by inhibiting multiple calcium channels (e.g., Arrang et al. 1985 Schlicker et al. 1994 Endou et al. 1994 Brown and Haas 1999 see Stark et al. 2004). For comparison, the signal transduction of soma-dendritic H3 autoreceptors in histamin-ergic neurons also involves a pertussis toxin-sensitive G-protein with subsequent inhibition of N- and P-type Ca2+ channels (Takeshita et al. 1998). The few exceptions to this signal transduction pathway are discussed in the corresponding subsections below (see Sections 3.1, 3.3, and 3.9). 

Arnsten AF, Cai JX, Steere JC, Goldman-Rakic PS (1995) Dopamine D2 receptor mechanisms contribute to age-related cognitive decline the effects of quinpirole on memory and motor performance in monkeys. J Neurosci 15 3429-39 Arrang JM, Garbarg M, Schwartz JC (1983) Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302 832-7 Arrang JM, Garbarg M, Schwartz JC (1985) Autoregulation of histamine release in brain by presynaptic H3-receptors. Neuroscience 15 553-62... 

Schlicker E, Fink K, Detzner M, Gothert M (1993) Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors. J Neural Transm Gen Sect 93 1-10 Schlicker E, Kathmann M, Detzner M, Exner HJ, Gothert M (1994) H3 receptor-mediated inhibition of noradrenaline release an investigation into the involvement of Ca2+ and K+ ions, G protein and adenylate cyclase. Naunyn Schmiedeberg s Arch Pharmacol 350 34 11 Schlicker E, Werthwein S, Zentner J (1999) Histamine H3 receptor-mediated inhibition of noradrenaline release in the human brain. Fundam Clin Pharmacol 13 120-2 Schmitz D, Gloveli T, Empson RM, Draguhn A, Heinemann U (1998) Serotonin reduces synaptic excitation in the superficial medial entorhinal cortex of the rat via a presynaptic mechanism. J Physiol 508 119-29... 

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