Heteroreceptor

Peripheral Cholinergic heteroreceptor -myenteric plexus Peripheral Vascular smooth muscle, autonomic terminals Peripheral autonomic and trigeminal nerve terminals Peripheral None identified ... 

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... 

Kalsner, S. (1990). Heteroreceptors, autoreceptors, and other terminal sites. In... 

G -protein-coupled receptors are often located on the presynaptic plasma membrane where they inhibit neurotransmitter release by reducing the opening of Ca2+ channels like inactivation and breakdown of the neurotransmitter by enzymes, this contributes to the neuron s ability to produce a sharply timed signal. An a2 receptor located on the presynaptic membrane of a noradrenaline-containing neuron is called an autoreceptor but, if located on any other type of presynaptic neuronal membrane (e.g., a 5-HT neuron), then it is referred to as a heteroreceptor (Langer, 1997). Autoreceptors are also located on the soma (cell body) and dendrites of the neuron for example, somatodendritic 5-HTia receptors reduce the electrical activity of 5-HT neurons. 

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. 

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. 

Dopamine acts on G-protein-coupled receptors belonging to the D1 -family of receptors (so-called D1-like receptors , or DlLRs, comprised of Dl- and D5-receptors), and the D2-family of receptors ( D2-like receptors , or D2LRs comprised of D2-, D3- and D4-receptors). Dl LRs stimulate adenylate cyclase activity and, possibly, also phosphoinosit-ide hydrolysis, while D2LRs reduce adenylate cyclase activity. In the striatum, DlLRs are predominately associated with medium spiny neurons of the direct pathway, while D2LRs have been found as autoreceptors on dopaminergic terminals, as heteroreceptors on cholinergic interneurons, and on indirect pathway neurons. In the SNr, DlLRs are located on terminals of the direct pathway projection, while D2LRs appear to function as autoreceptors. 

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. 

Serotonin 5-HT1A Human cDNA Alzheimer s disease, anxiety, depression, schizophrenia, hypertension, inflammation, pain, migraine, spasticity ulcers, obesity glaucoma Somatodendritic autoreceptor in hippocampus and raphe nuclei, circadian rhythm, somatodendritic heteroreceptor at cholinergic terminals of myenteric plexus... 

Membrane-bound receptors bind the intrinsic neurotransmitter (autoreceptor) or transmitters of neighboring neurons (heteroreceptor) and affect the cell via intracellular messengers. One response, for example, is the modulation of neurotransmitter release (Tanger, 1997). 

INHIBITION OF NEUROTRANSMITTER RELEASE BY PRESYNAPTIC SEROTONIN HETERORECEPTORS... 

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

Table 6-4 Autoreceptor, Heteroreceptor, and Modulatory Effects in Peripheral Synapses.1...

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). 

FIGURE 5—43. Shown here are the alpha 2 presynaptic heteroreceptors on serotonin axon terminals. 

FIGURE 5—44. This figure shows how norepinephrine can function as a brake for serotonin release. When norepinephrine is released from nearby noradrenergic neurons, it can diffuse to alpha 2 receptors, not only to those on noradrenergic neurons but as shown here, also to these same receptors on serotonin neurons. Like its actions on noradrenergic neurons, norepinephrine occupancy of alpha 2 receptors on serotonin neurons will turn off serotonin release. Thus, serotonin release can be inhibited not only by serotonin but, as shown here, also by norepinephrine. Alpha 2 receptors on a norepinephrine neuron are called autoreceptors, but alpha 2 receptors on serotonin neurons are called heteroreceptors. 

Axoaxonic interactions (noradrenergic axons with serotonergic axon terminals) Inhibitory alpha 2 heteroreceptors (negative feedback)... 

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