Neurotransmitter receptors types

Of the several classes of receptors for endogenous chemical signals [3], two are used as postsynaptic receptors in synaptic transmission ligand-gated ion channels (LGICs) and G protein-coupled receptors (GPCRs Fig. 1). Due to the large number of transmitters and the existence of several receptor types for almost all, postsynaptic receptor activation is the most diversified step of synaptic transmission. Table 1 shows selected neurotransmitter receptors. 

It is often valuable to classify receptors according to their mechanism of action, because this is intimately related to structure. The neurotransmitter receptors in the brain are of two main types classified according to their structure and mechanism of action ... 

G proteins regulate intracellular concentrations of second messengers. G proteins control intracellular cAMP concentrations by mediating the ability of neurotransmitters to activate or inhibit adenylyl cyclase. The mechanism by which neurotransmitters stimulate adenylyl cyclase is well known. Activation of those neurotransmitter receptors that couple to Gs results in the generation of free G(IS subunits, which bind to and thus directly activate adenylyl cyclase. In addition, free Py-subunit complexes activate certain subtypes of adenylyl cyclase (see Ch. 21). A similar mechanism appears to be the case for G(IO f, a type of G protein structurally related to G that is enriched in olfactory epithelium and striatum (Ch. 50). 

As described above, ondansetron has potent and highly selective antagonist properties at the 5-HT3-receptor [7]. The selectivity of action of ondansetron for the 5-HT3 receptor has been demonstrated using a number of in vitro preparations which respond to activation of a number of different neurotransmitter receptors. The selectivity ratio for ondansetron on 5-HT3-recep-tors compared with other receptor types is greater than 1000. In animals and in man, ondansetron has no overt actions on cardiovascular parameters and there are no effects on normal behaviour [7]. 

There is another reason why medications exert multiple effects. For example, an antidepressant that very specifically promotes serotonin neurotransmission and has little or no interaction with other receptor types will still produce multiple effects. How can this be Remember that in different areas of the brain, a single neurotransmitter can assume very distinct roles. When an individual takes a medication that alters the activity of a particular neurotransmitter, it generally does so throughout the brain. Consequently, the dopamine receptor blocking effect of haloperidol (Haldol) reduces hallucinations and paranoia in one brain region but causes upper extremity stiffness through its action in another brain region. 

What Is a Side Effect This chapter picks up where Chapters 1 and 2 left off. As we discussed in the earlier chapters, all medications, psychiatric and otherwise, have multiple effects. One takes a medication to achieve a therapeutic effect. Occasionally, a single medication may have more than one therapeutic effect. All other effects are side effects. Different medications may have differing therapeutic and side effects depending on the intended use. For example, trazodone and quetiapine are often prescribed to aid in sleep, and in this instance sedation is the desired effect, yet when used as an antidepressant and antipsychotic, respectively, the sedation is often an unwanted effect. Psychotropic medications typically have multiple effects. First, they usually interact with more than one nerve cell protein, be it a transporter or a receptor. Quite often, one of the medication s receptor or transporter interactions produces the therapeutic effect. The other interactions tend to not be involved in the therapeutic effect and only serve to produce side effects. Sometimes a neurotransmitter will have multiple different receptor types, but the medication interacts with... 

The concept of chemical transmission in the nervous system arose in the early years of the century when it was discovered that the functioning of the autonomic nervous system was largely dependent on the secretion of acetylcholine and noradrenaline from the parasympathetic and sympathetic nerves respectively. The physiologist Sherrington proposed that nerve cells communicated with one another, and with any other type of adjacent cell, by liberating the neurotransmitter into the space, or synapse, in the immediate vicinity of the nerve ending. He believed that transmission across the synaptic cleft was unidirectional and, unlike conduction down the nerve fibre, was delayed by some milliseconds because of the time it took the transmitter to diffuse across the synapse and activate a specific neurotransmitter receptor on the cell membrane. 

There are two major types of receptor which are activated by neurotransmitters. These are the ionotropic and metabotropic receptors. The former receptor type is illustrated by the amino acid neurotransmitter receptors for glutamate, gamma-aminobutyric acid (GABA) and glycine, and the acetylcholine receptors of the nicotinic type. These are examples of fast transmitters in that they rapidly open and close the ionic channels in... 

The S-enantiomer of citalopram (escitalopram) is over 100 times more potent in inhibiting the reuptake of 5-HT into brain slices than the R-form and is devoid of any activity at the neurotransmitter of other receptor types (racemic citalopram has an affinity for histamine receptors and causes sedation). In in vivo studies, escitalopram is more potent than the R-form or the racemate in releasing 5-HT in the cortex of conscious rats it has been... 

The dopamine beta-hydroxylase (Dbh) gene is necessary for the production of NE and epinephrine. Disruption of this gene results in the absence of NE and epinephrine production and is therefore used in studies determining the roles of these neurotransmitters. This approach is favored over the knockout of adrenergic receptors because of the multiplicity of receptor types for NE and epinephrine. 

The effect of the release of any neurotransmitter depends on the type of receptor that it binds. One challenge in understanding serotonergic function in the brain is that at least 18 subtypes of serotonin receptors have so far been found, each with its own mechanism of action. Scientists have debated the reasons for this extreme number of types of receptor for one neurotransmitter (serotonin outnumbers most other neurotransmitters in this regard). It has been suggested that this diversity allows for more complicated signaling between brain cells that could not occur with just one or two receptor types. As a result, communication between cells is not simply... 

Carbamazepine produces complex effects in a variety of neurotransmitters, receptors, and second messenger and neuropeptide systems (Post et al. 1992, 1994a). Determining which of these effects is most closely associated with its psychotropic properties in bipolar disorder and which of these or other effects may be responsible for the augmentation response in combination therapy with dihydropyridine L-type CCBs remains to be further evaluated. However, discussion of two possibilities might be beneficial. One possibility, of course, is that actions of carbamazepine unrelated to calcium dynamics account for its augmenting effects with nimodipine. The plethora of these other... 

Cross AJ, Crow TJ, Johnson JA Studies on neurotransmitter receptor systems in cortex and hippocampus in senile dementia of the Alzheimer type. J Neurol Sci 64 109-117, 1984... 

Huganir RL, Greengard P Regulation of neurotransmitter receptor desensitization by protein phosphorylation. Neuron 5 555-567, 1990 Hughes J, Boden P, Costall B, et al Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci U S A 87 6728-6732, 1990... 

There are three principal classes of opiate receptors, designated x, K, and 5, and there exist a number of drugs that are specific for each of these receptor types. However, most of the clinically used opiates are quite selective for the preceptor the endogenous opiates enkephalin, endorphin and dynorphin are selective for the p and 5, 5 and k receptors respectively. When activated by opioids these receptors produce biochemical signals that block neurotransmitter release from nerve terminals, a process that underlies their blockade of pain signaling pathways as well as other effects, such as constipation, diuresis, euphoria, and feeding. 

Acetylcholine (ACh) is an example of an endogenous neurotransmitter that binds to more than one receptor type, the nicotinic acetylcholine receptor (nAChR) which preferentially binds nicotine and the muscarinic receptor which binds muscarine, a mushroom alkaloid. The latter is a G protein-coupled receptor while the nACh receptor is an excitatory ligand-gated ion channel that transports Na-i- ions. Nicotinic cholinergic receptors are found in the CNS, autonomic ganglia, and at the neuromuscular junction of skeletal muscles. They are a possible target for anaesthetics. 

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