Heteroreceptors histamine

Studies have now started to clarify the role of histamine Hi and H2 receptors in the cardiovascular manifestations of anaphylaxis. However, histamine can activate H3 and H4 receptors [56, 57]. Levi and coworkers [58-60] identified H3 receptors as inhibitory heteroreceptors in cardiac adrenergic nerve endings. This suggests a mechanism by which endogenous histamine can activate norepinephrine release in normal and ischemic conditions [61,62]. The functional identification ofH3 receptors in the human heart [59] means that these receptors might be directly and/or indirectly involved in the cardiovascular manifestations of anaphylactic reactions. 

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... 

Histaminergic neurons can regulate and be regulated by other neurotransmitter systems. A number of other transmitter systems can interact with histaminergic neurons (Table 14-1). As mentioned, the H3 receptor is thought to function as an inhibitory heteroreceptor. Thus, activation of brain H3 receptors decreases the release of acetylcholine, dopamine, norepinephrine, serotonin and certain peptides. However, histamine may also increase the activity of some of these systems through H, and/or H2 receptors. Activation of NMDA, p opioid, dopamine D2 and some serotonin receptors can increase the release of neuronal histamine, whereas other transmitter receptors seem to decrease release. Different patterns of interactions may also be found in discrete brain regions. 

Schwartz, J.C.,Arrang, J. M., Garbarg, M., Gulat-Marnay, C. and Pollard, H. Modulation of histamine synthesis and release in brain via presynaptic autoreceptors and heteroreceptors. Ann. N.Y.Acad. Sci. 604 40-54,1990. 

Schlicker, E., Malinowska, B., Kathmann, M. and Gothert, M. Modulation of neurotransmitter release via histamine H3 heteroreceptors. Fundam. Clin. Pharmacol. 8 128-137,1994. 

Mirtazapine enhances central noradrenergic and serotonergic activity through the antagonism of central presynaptic a2-adrenergic autoreceptors and heteroreceptors. It also antagonizes 5-HT2 and 5-HT3 receptors. It also blocks histamine receptors. 

The term "H3 receptor" has been coined by Arrang et al.1 H3 receptors are located on paracrine cells and on neurones activation of H3 receptors usually causes inhibition of the release of the respective mediator or neurotransmitter. The receptor characterized by Arrang et al.1 is an example of an autoreceptor, i.e. of a receptor via which the transmitter released from a given neurone influences its own release. H3 receptor-mediated inhibition of the release of transmitters other than histamine has also been described such receptors are known as heteroreceptors. The present review will focus on H3 heteroreceptors in the central nervous system (CNS) in separate chapters of this book, H3 autoreceptors, H3 heteroreceptors in the neuroendocrine system as well as H3 receptor-mediated modulation of transmitter release in vivo will be considered. A separate article will also deal with H3 heteroreceptors in peripheral tissues although an example of an H3 receptor in the retina will be covered in our chapter, due to the close relationship between CNS and retina2. 

Standard superfusion and electrophysiological techniques do not allow to decide whether an H3 heteroreceptor involved in the inhibition of release of a given transmitter is actually located presynaptically (i.e. on the axon terminals) of the respective neurone. Recent (unpublished) data from our laboratory may serve to illustrate this point. In guinea-pig cerebral cortex slices, noradrenaline release is inhibited by histamine via H3 receptors and facilitated via H2 receptors. Using an appropriate technique (see next paragraph) we found that only the H3 but not the H2 receptor is located presynaptically. 

Histamine H3 receptors are not only involved in the inhibition of the release of histamine itself ("autoreceptors") but, in addition, also in the inhibition of the release of other neurotransmitters ("heteroreceptors"). Such an H3 heteroreceptor-mediated... 

Schlicker E (1997) Histamine H3 heteroreceptors in the CNS. In Neurobiology of Histamine (G Prell ed) Humana Press, Totowa, NJ, USA, in press. 

MODULATION OF CATECHOLAMINES AND SEROTONIN RELEASE MEDIATED BY HISTAMINE H3 HETERORECEPTORS... 

Involvement of histamine H3 receptors as heteroreceptors in learning and memory... 

Histamine H3-receptors have been reported to regulate not only the release and turnover of histamine via autoreceptors on histaminerglc nerve endings [1-3], but also the releases of noradrenaline, dopamine, serotonin, and acetylcholine via heteroreceptors on non-histaminerglc axon terminals [22-26], Thioperamide increased the release of these neurotransmitters, while... 

In relation to the monoaminergic systems we observed that clobenpropit increased turnover rate of noradrenaline only in some brain regions (17), although histamine H3 heteroreceptors modulate the releases of noradrenaline, dopamine, and serotonin [23-26]. Thus, it appears that the contribution of histamine H3 hetero receptors on the modulation of monoaminergic neurotransmitters may be minor, just being similar to the cholinergic system. 

Abstract Presynaptic receptors for dopamine, histamine and serotonin that are located on dopaminergic, histaminergic and sertonergic axon terminals, respectively, function as autoreceptors. Presynaptic receptors also occur as heteroreceptors on other axon terminals. Auto- and heteroreceptors mainly affect Ca2+-dependent exocytosis from the receptor-bearing nerve ending. Some additionally subserve other presynaptic functions. 

Blockade of histamine autoreceptors increases histamine synthesis and release and may support higher CNS functions such as arousal, cognition and learning. Peripheral histamine heteroreceptors on C liber and on postganglionic sympathetic fiber terminals diminish neuropeptide and noradrenaline release, respectively. Both inhibititory effects are beneficial in myocardial ischemia. The inhibition of neuropeptide release also explains the antimigraine effects of some agonists of presynaptic histamine receptors. 

Our knowledge of presynaptic dopamine and serotonin receptors dates back to the 1970s (Famebo and Hamberger 1971). Presynaptic histamine receptors were discovered in 1983 (Arrang et al. 1983). Presynaptic dopamine receptors occur as autoreceptors, i.e., on dopaminergic axon terminals, and as heteroreceptors on nondopaminergic axon terminals. By analogy the same holds true for presynaptic histamine and serotonin receptors. The early days of the dopamine autoreceptors were stormy, but the controversies were finally solved (see Starke et al. 1989). The main function that presynaptic receptors affect is transmitter release, which in this article means Ca2+-dependent exocytosis. However, some receptors discussed in... 

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... 

They were the first presynaptic H3 heteroreceptors to be discovered (in guinea pig mesenteric artery Table 1). They mediate inhibition of transmitter release from many noradrenergic neurons, peripheral as well as central (Table 1). They may be activated by histamine from mast cells, as happens in the heart upon myocardial ischemia (see Section 3.10). In the CNS an input of endogenous histamine has not been demonstrated (see references in Table 3). For example, the release of noradrenaline in the hippocampus of freely moving rats remained unchanged upon local... 

H3 receptor activation inhibits the release of serotonin in several rat brain regions (Table 3). An endogenous histamine tone has been found at the heteroreceptors in rat brain cortex (Schlicker et al. 1988 Fink et al. 1990). At high micromolar concentrations histamine may enhance the release of serotonin (and of noradrenaline) via a tyramine-like mechanism (Starke and Weitzell 1978 Young et al. 1988). 

The inhibitory H3 heteroreceptors on dopaminergic nerve terminals in mouse striatal slices were not activated by endogenous histamine under the experimental conditions chosen, since their blockade did not enhance the release of dopamine (Schlicker et al. 1993). In the rat nucleus accumbens in vivo, however, indirect evidence (an histamine-evoked increase in acetylcholine release) suggests that dopamine release is permanently inhibited by endogenous histamine (Prast et al. 1999a see Section 3.6). 

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