Heteroreceptors regulation

Presynaptic receptor A receptor, either an autoreceptor or heteroreceptor, located on the presynaptic neuronal membrane which regulates the release of the neurotransmitter. 

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. 

P. M. Laduron (1985). Postsynaptic heteroreceptors in the regulation of nenronal transmission. Biochem. Pharmacol. 34 467-470. 

Control of transmitter release is not limited to modulation by the transmitter itself. Nerve terminals also carry regulatory receptors that respond to many other substances. Such heteroreceptors may be activated by substances released from other nerve terminals that synapse with the nerve ending. For example, some vagal fibers in the myocardium synapse on sympathetic noradrenergic nerve terminals and inhibit norepinephrine release. Alternatively, the ligands for these receptors may diffuse to the receptors from the blood or from nearby tissues. Some of the transmitters and receptors identified to date are listed in Table 6-4. Presynaptic regulation by a variety of endogenous chemicals probably occurs in all nerve fibers. 

A heteroreceptor is a receptor regulating the synthesis and/or the release of mediators other than its own ligand (IUPAC). 

When studying the role of various H3 receptor compounds on pituitary hormone secretion some points have to be considered a) are the actions of the compounds related to H3 receptor binding or to a non-specific action, b) are the actions related to an auto- or heteroreceptor or eventually postsynaptic receptor effect of the compounds, and c) are the actions related to an effect known to involve histaminergic neurons. In the following, we will give a short description of the effect of HA in the neuroendocrine regulation of pituitary hormone secretion (Table 1) and focus on the role of H3 receptors in modulation of the secretion of the individual pituitary hormones based on previously published investigations and our own recent experiments. 

However, receptor autoradiography and in vitro studies have suggested that H3 receptors are located on other aminergic neurons in the brain. Since amines such as serotonin and catecholamines are involved in the regulation of pituitary hormone secretion, it is obvious that an action of the H3 receptor compounds may be exerted via these H3 heteroreceptors. Only few studies have evaluated this heteroreceptor action. It has been excluded that the effect of the H3 receptor agonists is due to an effect on H3 receptors located on serotonergic neurons, while an effect on catecholaminergic neurons has yet not been excluded. 

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... 

The HA H3 receptor is further localized on the histaminergic nerve terminals in the brains of rats.40 41-4346 Of the three subclasses of HA receptor that have been identified in the brain, the Hi and H2 receptors are thought to be exclusively post-synaptic.4649 The H3 receptor found on the histaminergic nerve terminal was defined as an autoreceptor and is thus a HA receptor subtype that is uniquely positioned to regulate the amount of HA synthesized and released from the HA neurons.45- 60 Moreover, the presence of H3 receptors on several non-histaminergic nerve terminals (heteroreceptors) has now been further established. Modulation of neurotransmitter... 

Laduron PM (1985) Presynaptic heteroreceptors in regulation of neuronal transmission. Biochem Pharmacol 34 467-470... 

Morikawa H, Manzoni OJ, Crabbe JC, Williams JT (2000) Regulation of central synaptic transmission by 5-HTis auto- and heteroreceptors. Mol Pharmacol 58 1271-8 Morisset S, Rouleau A, Ligneau X, Gbahou F, Tardivel-Lacombe J, Stark H, Schunack W, Ganellin CR, Schwartz JC, Arrang JM (2000) High constitutive activity of native H3 receptors regulates histamine neurons in brain. Nature 408 860-4... 

The review by Cartmell and Schoepp (2000) covered almost exhaustively the field of mGluRs that are localized on nonglutamatergic terminals and regulate as presynap-tic heteroreceptors the release of various transmitters this section of my chapter will therefore be essentially restricted to recent aspects of the functional pharmacology of presynaptic metabotropic glutamate heteroreceptors. 

The original observations made in the early 1970s led to the hypothesis that neurotransmitter release was regulated at the level of the nerve terminals by presynaptic auto- and heteroreceptors. These discoveries were confirmed and extended... 

Morikawa H, Manzoni OJ, Crabbe JC, Williams JT. Regulation of central synaptic transmission by 5-HT1B auto- and heteroreceptors. Mol Pharmacol 2000 58 1271-1278. 

Additional neuropharmacological changes that may contribute to the clinical effects of tricyclic antidepressants include indirect facihtation of 5-HT (and perhaps DA) neurotransmission through excitatory heteroreceptors on other monoaminergic neurons, or desensitized, inhibitory autoreceptors, as well as D autoreceptors. Activated release of 5-HT and DA may, in turn, lead to secondary down-regulation of 5-HTj autoreceptors, postsynaptic S-HT receptors, and perhaps D autoreceptors and postsynaptic Dj receptors. 

Finally, the atypical antidepressants mirtazapine and mianserin are structural analogs of 5-HT with potent antagonistic effects at several postsynaptic 5-HT receptor types (including 5-HT, 5-HT2U and 5-HT receptors) and can produce gradual down-regulation of 5-HT receptors. Mirtazapine limits the effectiveness of inhibitory adrenergic heteroreceptors on sero-... 

Intercellular communication in the nervous system is typically mediated through synaptic transmission via the release of neurotransmitters and their subsequent binding to specific receptors. The transmitter-receptor interaction then elicits changes in ion channel permeability and/or second messenger formation in the innervated cell. Neurotransmitters can also interact with receptors located on the presynaptic terminal (either autoreceptors, which are activated by the same transmitter, or heteroreceptors, which are activated by a different transmitter released by a different neuron) to regulate the presynaptic function, often by influencing neurotransmitter release. Termination of synaptic neurotransmission depends upon the removal of neurotransmitter molecules from the synaptic cleft by either enzymatic degradation or by reuptake into the presynaptic terminal. 

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