Neurotransmitters action

Traditionally receptors have been classified according to their pharmacology. Each neurotransmitter acts on its own family of receptors and these receptors show a high degree of specificity for their transmitter. Thus, the receptors on which acetylcholine (ACh) works do not respond to glutamate (or any other neurotransmitter) and vice versa. Diversity of neurotransmitter action is provided by the presence of multiple receptor subtypes for each neurotransmitter, all of which still remain specific to that neurotransmitter. This principle is illustrated by the simple observations outlined in... 

McCormick, DA (1992) Neurotransmitter actions in the thalamus and cerbral cortex and their role in neuromodulation of thalamocortical activity. Prog. Neurobiol. 39 3778-3788. Moruzzi, G and Mayoun, HW (1949) Brainstem reticular formation and activation of the EEG. EEG Clin. Neurophysiol. 1 455-473. 

Regardless of the underlying etiology, all seizures involve a sudden electrical disturbance of the cerebral cortex. A population of neurons fires rapidly and repetitively for seconds to minutes. Cortical electrical discharges become excessively rapid, rhythmic, and synchronous. This phenomenon is presumably related to an excess of excitatory neurotransmitter action, a failure of inhibitory neurotransmitter action, or a combination of the two. In the individual patient, however, it is usually impossible to identify which neurochemical factors are responsible. 

Unwin, N., Neurotransmitter action opening of ligand-gated ion channels, Neuron, 10(Suppl. 1), 31 —41, 1993. 

Unwin, N. (1993) Neurotransmitter action opening of a ligand-gated channel. Neuron 10 Suppl., 31-41. 

Over 100 years ago, a debate was raging between the two most famous neuroscientists in the world concerning the nature of the nervous system. Golgi believed that all neurons were connected in a nerve net or syncytium whereas Ramon y Cajal believed that neurons were separated from each other by tiny spaces called synapses. Cajal proved to be correct, and it was later learned that neurons communicate across the synapse by releasing chemical substances known as neurotransmitters or by releasing electrical charges. Because chemical neurotransmission is much more common than electrical transmission, especially in the brain, and it is chemical neurotransmission that is modulated by psychiatric medicines, our discussion will focus on the chemotransmitter process. In simplest terms, the process of chemical neurotransmission occurs in three steps neurotransmitter production, neurotransmitter release, and neurotransmitter action on specific receptors. 

The penis is mainly supplied by the internal pudendal artery, and three major sets of veins, superficial, intermediate, and deep veins, drain it. Drug-induced changes in neurotransmitter action can affect local blood flow. Vascular supply, intrinsic smooth muscles of the penis, and adjacent striated muscles are controlled by nerves arising from the thoracolumbar sympathetic, the lumbosacral parasympathetic, and the lumbosacral somatic systems. The pudendal nerve is the major somatic pathway innervating the male genitalia. 

Because body fluids are remote from many relevant sites of neurotransmitter action and confounded by multiple events, it is all the more impressive when substantial consistency in results is seen. 

A neurotransmitter is a chemical messenger that mediates the passage of electrical information from one neuron to an adjacent neuron. To be defined as a classical neurotransmitter, a molecule must be synthesized and stored in a neuron, released from that neuron in a Ca dependent process, diffuse to an adjacent neuron, specifically dock with a receptor on that adjacent neuron, and have its binding to this receptor blocked by a competitive antagonist. A neuromodulator, on the other hand, is a molecule which is present in the synaptic cleft and which modifies either the frequency or the efficiency of the neurotransmitter molecule, thereby either amplifying or attenuating the neurotransmitter action. 

Unwin, N. Neurotransmitter action Opening of ligand-gated ion channels (1993) Cell 72, 31-41... 

The known or suspected neurotransmitters in the brain already number several dozen (Table 1-1). Based on theoretical considerations of the amount of genetic material in neurons, there may be several hundred to several thousand unique brain chemicals. Originally, about half a dozen classical neurotransmitters were known. In recent years, an ever increasing number of neurotransmitters are being discovered. The classical neurotransmitters are relatively low molecular weight amines or amino acids. Now we know that strings of amino acids called peptides can also have neurotransmitter actions, and many of the newly discovered neurotransmitters are peptides, which are specifically called neuropeptides (Fig. 1-9). 

Dual neurotransmitter action at both serotonin and norepinephrine is possible only by combining two different psychopharmacological agents simultaneously. 

The neurotransmitter action of epinephrine is terminated by reuptake into the neuron that released it, or breakdown to inactive metabolites by the enzymes catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO). The second messenger effects inside the cell are terminated by enzymes that break down cAMP, and by phosphatases that reverse the action of the kinases by removing phosphates. 

One of the major problems in thinking about dopamine neurotransmission is the number of features which do not fit into the textbook model of classical synaptic transmission, based on the neuromuscular junction. These include an extremely wide divergence of release sites of a single axon, extrasynaptic location of receptors, termination of neurotransmitter action by diffusion and uptake from extrasynaptic sites, and significant overflow of neurotransmitter from the synaptic cleft into the extracellular space. 

As opposed to the two other endogenous excitatory amino acid candidates, cystelc acid and cysteine sulphinlc acid (15), glutamate (16) and aspartate (13) are found in abundant quantities in the mammalian CNS. Metabolically, aspartate and glutamate are related and their metabolism is quite complex. Thus, there are undoubtedly several metabolic pools of glutamate and aspartate, in addition to any neurotransmitter pool, making it difficult to study the biochemical aspects of their neurotransmitter action. Nevertheless, it has been shown that both substances are accumulated into brain tissue by a high affinity process, and that both can be released from brain tissue by electrical field stimulation. This behavior is characteristic of neurotransmitters. 

McCormick DA (1992) Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog Neurobiol 39 337-388. 

What do these receptors do Like other cell membrane receptors they may induce both rapid and slower responses. The rapid responses may result from transmembrane flow of ions, just as in neurotransmitter action (Figs. 30-19,30-20). The first response observed is an oxidative burst, which within minutes generates reduced oxygen intermediates (ROIs pp. 

B. Mechanisms of Antidepressant Action Potential sites of action of antidepressants at central nervous system synapses are shown in Figure 30-2. By means of several mechanisms, almost all antidepressants result in a potentiation of the neurotransmitter actions of norepinephrine, serotonin, or both. The only exception is bupropion, which has an unknown mechanism of action. Long-term use of tricyclics and MAOIs, but not SSRIs, leads to down-regulation of beta receptors. 

Tricyclic antidepressants The acute effect of tricyclic drugs is to inhibit the reuptake mechanisms (transporters) responsible for the termination of the synaptic actions of both NE and 5-HT in the brain. This results in potentiation of their neurotransmitter actions at postsynaptic receptors. 

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