Autoreceptors neurotransmitter

Starke, K (1987) Presynaptic a-autoreceptors. Rev. Physiol. Biochem. Pharmacol. 107 73-146. Zhong, H and Minneman, KP (1999) i-Adrenoceptor subtypes Eur. J. Pharmacol. 375 261-276. Zigmond, RE, Schwarzschild, MA and Rittenhouse, AR (1989) Acute regulation of tyrosine hydroxylase by nerve activity and by neurotransmitters via phosphorylation. Ann. Rev. Neurosci. 12 451-461. 

Figure 20.1 Schematic diagram illustrating how antidepressants increase the concentration of extraneuronal neurotransmitter (noradrenaline and/or 5-HT). In the absence of drug (b), monoamine oxidase on the outer membrane of mitochondria metabolises cytoplasmic neurotransmitter and limits its concentration. Also, transmitter released by exocytosis is sequestered from the extracellular space by the membrane-bound transporters which limit the concentration of extraneuronal transmitter. In the presence of a MAO inhibitor (a), the concentration of cytoplasmic transmitter increases, causing a secondary increase in the vesicular pool of transmitter (illustrated by the increase in the size of the vesicle core). As a consequence, exocytotic release of transmitter is increased. Blocking the inhibitory presynaptic autoreceptors would also increase transmitter release, as shown by the absence of this receptor in the figure. In the presence of a neuronal reuptake inhibitor (c), the membrane-bound transporter is inactivated and the clearance of transmitter from the synapse is diminished...

ACh regulates the cortical arousal characteristic of both REM sleep and wakefulness (Semba, 1991, 2000 Sarter Bruno, 1997, 2000). Medial regions of the pontine reticular formation (Figs. 5.2 and 5.7) contribute to regulating both the state of REM sleep and the trait of EEG activation. Within the medial pontine reticular formation, presynaptic cholinergic terminals (Fig. 5.1) that release ACh also are endowed with muscarinic cholinergic receptors (Roth et al, 1996). Autoreceptors are defined as presynaptic receptors that bind the neurotransmitter that is released from the presynaptic terminal (Kalsner, 1990). Autoreceptors provide feedback modulation of transmitter release. Autoreceptor activation... 

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. 

The postsynaptic receptors on any given neuron receive information from transmitters released from another neuron. Typically, postsynaptic receptors are located on dendrites or cell bodies of neurons, but may also occur on axons or nerve terminals in the latter case, an axoaxonic synaptic relationship may cause increases or decreases in transmitter release. In contrast, autoreceptors are found on certain neurons and respond to transmitter molecules released from the same neuron. Autoreceptors may be widely distributed on the surface of the neuron. At the nerve terminal, they respond to transmitter molecules released into the synaptic cleft on the cell body, they may respond to transmitter molecules released by dendrites. Functionally, most autoreceptors appear to decrease further transmitter release in a kind of negative feedback loop. Autoreceptors have been identified for all the catecholamines, as well as for several other neurotransmitters. a2-adrenergic receptors are often found on noradrenergic nerve terminals of postganglionic sympathetic nerves, as well as on noradrenergic neurons in the CNS [36], and activation of these receptors decreases further norepinephrine release. Dopamine autoreceptors,... 

The chief direct mechanism of the methyixanthines is the antagonism of adenosine receptors (Snyder and Sklar 1984). Adenosine is an inhibitory neurotransmitter, acting at inhibitory presynaptic autoreceptors. At... 

Negative Feedback. Some of the neurotransmitter diffuses back to the surface of the nerve cell that released it. There are also receptors that tit the neurotransmitter here. When a neurotransmitter binds a receptor (called an autoreceptor) at the axon terminal of the nerve cell that released it, it tells the nerve cell that there s plenty of neurotransmitter already in the synapse. So don t release anymore This process is called negative feedback and is analogous to the way a thermostat works in your home to control room temperature. 

In addition to the posts)maptic receptors, dopamine autoreceptors also exist on the nerve terminals, dendrites and cell bodies. Experimental studies have shown that stimulation of the autoreceptors in the somatodendritic region of the neuron slows the firing rate of the dopaminergic neuron while stimulation of the autoreceptors on the nerve terminal inhibits both the release and the synthesis of the neurotransmitter. Structurally, the autoreceptor appears to be of the D2 type. While several experimental compounds have been developed that show a high affinity for the autoreceptors, to date there is no convincing evidence for their therapeutic efficacy. 

Of the many drugs that have been developed which modulate GABA function, the inhibitors of GABA transaminase have been shown to be effective anticonvulsants. These are derivatives of valproic acid that not only inhibit the metabolism of GABA but may also act as antagonists of the GABA autoreceptor and thereby enhance the release of the neurotransmitter. GABA-uptake inhibitors have also been developed (for example, derivatives... 

Noradrenaline is the neurotransmitter most closely associated with the peripheral and central stress response (Figure 9.5). There is experimental evidence to show that drugs such as yohimbine that block the noradrenergic autoreceptors (e.g. on cell bodies and nerve terminals) and thereby enhance noradrenaline release cause fear and anxiety in both man and animals. Conversely, drugs that stimulate these autoreceptors (as exemplified by clonidine) diminish the anxiety state because they reduce the release of noradrenaline. Benzodiazepines have been shown to inhibit the fear-motivated increase in the functional activity of noradrenaline in experimental animals, but it is now widely believed that the action of the benzodiazepines on the central noradrenergic system is only short term and may contribute to the sedative effects which most conventional benzodiazepines produce, at least initially. Nevertheless, altered noradrenergic... 

Starke K, Gothert M, Kilbinger H. Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 1989 69 864-989. 

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). 

The nervous system has several ways to maintain a stable and constant environment, called homeostasis. Autoreceptors are a form of feedback inhibition, which help maintain homeostasis. When a neuron is excited, it can release neurotransmitters into the synapse that activate receptors on neighboring cells, communicating information through the nervous system. When a neurotransmitter is released, it also binds to receptors on the neuron that released it, which serves to inhibit further release. In this way, neurons can r ulate their own release, so that they don t release too much neurotransmitters into the brain, which might overexcite or overinhibit neighboring neurons or deplete the neuron s own store of neurotransmitters. 

FIGURE 6-35. Mechanism of action of serotonin selective reuptake inhibitors (SSRIs)—part 1. Depicted here is a serotonin neuron in a depressed patient. In depression, the serotonin neuron is conceptualized as having a relative deficiency of the neurotransmitter serotonin. Also, the number of serotonin receptors is up-regulated, or increased, including presynaptic autoreceptors as well as postsynaptic receptors. 

Hallucinogens have rather complex interactions at neurotransmitter systems, but one of the most prominent is a common action as agonists at serotonin 2A (5HT2A) receptor sites (Fig. 13—10). Hallucinogens certainly have additional effects at other 5HT receptors (especially 3HT1A somatodendritic autoreceptors) and also at other neurotransmitter systems, especially norepinephrine and dopamine, but the relative importance of these other actions are less well known. Also, MDMA appears to be a powerful releaser of serotonin and it and several drugs structurally related to it... 

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. 

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... 

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