Receptor, postsynaptic

The principal arninoglycoside toxicides are neuromuscular paralysis, ototoxicity, and nephrotoxicity. Neuromuscular paralysis is a relatively rare complication resulting from high aminoglycoside concentrations at the neuromuscular junctions following, for example, rapid bolus intravenous injection or peritoneal instillation, rather than the normal intravenous infusion. The mechanism apparentiy involves an inhibition of both the presynaptic release of acetylcholine and the acetylcholine postsynaptic receptors (51). 

Psychostimulants. Figure 2 Dopamine molecules have two different possible targets. Both ways are initially increased by DAT inhibition caused by methylphenidate pre- and postsynaptic dopamine receptors. Stimulation of postsynaptic receptors results in inhibition of presynaptic action potential generation. On the other hand, presynaptic receptor stimulation leads to a transmission inhibition of action potentials. Therefore, both mechanisms are responsible for a decrease in vesicular depletion of dopamine into the synaptic cleft (adapted from [2]). 

Reuptake transporters are structures within the cell membranes of the presynaptic nerve terminal that serve to transport biogenic amines released from vesicles back into the nerve cell. These structures are targets for antidepressants, which block the transporter, thus increasing the bioavailability of neurotransmitters at postsynaptic receptors. 

There are numerous transmitter substances. They include the amino acids glutamate, GABA and glycine acetylcholine the monoamines dopamine, noradrenaline and serotonin the neuropeptides ATP and NO. Many neurones use not a single transmitter but two or even more, a phenomenon called cotransmission. Chemical synaptic transmission hence is diversified. The basic steps, however, are similar across all neurones, irrespective of their transmitter, with the exception of NO transmitter production and vesicular storage transmitter release postsynaptic receptor activation and transmitter inactivation. Figure 1 shows an overview. Nitrergic transmission, i.e. transmission by NO, differs from transmission by other transmitters and is not covered in this essay. 

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. 

At most synapses a conventional NT is synthesised from an appropriate precursor in the nerve terminal, stored in vesicles, released, acts on postsynaptic receptors and is... 

Many of the neuroleptics are a-adrenoceptor antagonists. Some, like chlorpromazine, block d postsynaptic receptors while clozapine (and risperidone) are as potent at 2 as D2 receptors. There is no evidence that either of these actions could influence striatal or mesolimbic function but NA is considered important for function of the prefrontal cortex and any increase in its release, achieved by blocking a2-mediated autoinhibition, might contribute to a reduction in negative symptoms and provide a further plus for clozapine (see Nutt et al. 1997). Centrally, however, most a2-receptors are found postsynaptically and their function, and the effect of blocking them, is uncertain. 

Figure 21.5 Mechanisms of opioid analgesia at the spinal level. Action potentials in nociceptive afferent fibres invade the terminal and by opening calcium channels (L, N and P-type) cause the release of glutamate and peptides that further transmit pain subsequent to activation of their postsynaptic receptors. Presynaptic opioid receptor activation (mu- and delta-mediated effects have been most clearly shown) opens potassium channels which hyperpolarise the terminal, so reducing transmitter release and inhibiting the postsynaptic neuron...

QUESTION In the absence of serotonin neurons, could MDMA still have a direct agonist action at postsynaptic receptors or is that 5-HT ... 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

Agonist drugs can also bind directly to the postsynaptic receptor, so mimicking the physiological effect of the neurotransmitter for example, morphine and heroin bind to the brain s opiate receptors and, thus, directly stimulate feelings of pleasure and pain... 

Once THC is bound to presynaptic and postsynaptic receptor sites, a way to stop its action is required. Otherwise, stimulation could continue indefinitely and a perpetual high could be maintained from just a few puffs of marijuana. Research has shown that the endogenous cannabinoid anandamide is deactivated by being removed from receptors and transported into the cell, where it is broken down by an enzyme into nonactive components. This process is believed to be the same for THC. 

The first two antidepressants, iproniazid and imipramine, were developed in the same decade. They were shown to reverse the behavioural and neurochemical effects of reserpine in laboratory rodents, by inhibiting the inactivation of these monoamine transmitters (Leonard, 1985). Iproniazid inhibits MAO (monoamine oxidase), an enzyme located in the presynaptic neuronal terminal which breaks down NA, 5-HT and dopamine into physiologically inactive metabolites. Imipramine inhibits the reuptake of NA and 5-HT from the synaptic cleft by their transporters. Therefore, both of these drugs increase the availability of NA and 5-HT for binding to postsynaptic receptors and, therefore, result in enhanced synaptic transmission. Conversely, lithium, the oldest but still most frequently used mood stabiliser (see below), decreases synaptic NA (and possibly 5-HT) activity, by stimulating their reuptake and reducing the availability of precursor chemicals required in the biosynthesis of second messengers. 

Postsynaptic receptor A receptor located on the postsynaptic neuronal membrane mediating the physiological effects of the neurotransmitter. 

Presynaptic vesicles are estimated to each contain approximately 3,000-5,000 transmitter molecules the internal volume of a vesicle is such that its internal transmitter concentration may be =0.5 mol/1 vesicle contents may be released within less than 1 ms and this occurs within <0.02 pm of the postsynaptic receptors. The space within... 

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,... 

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