Synaptic reaction

The human brain is comprised of many millions of interconnected units, known individually as biological neurons. Each neuron consists of a cell to which is attached several dendrites (inputs) and a single axon (output). The axon connects to many other neurons via connection points called synapses. A synapse produces a chemical reaction in response to an input. The biological neuron fires if the sum of the synaptic reactions is sufficiently large. The brain is a complex network of sensory and motor neurons that provide a human being with the capacity to remember, think, learn and reason. 

These cascades of reactions need time in the range of seconds synaptic transmission through GPCRs is slow. All further postsynaptic changes depend on the type of postsynaptic cell. For example activation of 32-adrenoceptors causes in the heart an increase of the rate and force of contraction in skeletal muscle glycogenolysis and tremor in smooth muscle relaxation in bronchial glands secretion and in sympathetic nerve terminals an increase in transmitter release. 

If immune reactions are to be avoided then recombinant human factor should be used and that cannot be produced in large quantities. In any case, it is a large protein that will have to be injected directly into the brain. Even if these problems can be overcome the spread and intensity of any NGF effect has to be restricted so that excessive neuritic growth and inappropriate increases in synaptic connections do not occur. 

Meffert, M. K., Calakos, N. C., Scheller, R. H. and Schulman, H. Nitric oxide modulates synaptic vesicle docking/fusion reactions. Neuron 16 1229-1236,1996. 

In this study we showed that the biochemical networks function according to the mode of connection between the basic systems (e.g., network A, B, or C), and also according to the processing performed at each neuron (i.e., reaction mechanism or kinetic constants). For the biochemical systems, the strengths of connection between basic elements (i.e., synaptic weights) is represented by the concentration of the component that is shared between the neurons. 

In summary, the release of nenrotransmitter from a presynaptic neurone into a synaptic cleft occurs via the process of exocytosis, which is regulated by the increase in Ca " ion concentration in the presynaptic terminal. The increase in Ca " ion concentration is achieved by release of Ca " ions by opening of the Ca ion channel in the endoplasmic reticulum, which is controlled by the concentration of IP3. Failure to release inositol from the inositol phosphates reduces the free inositol concentration, which interferes in the synthesis of PIP2. The phospholipase no longer catalyses a zero order reaction. Consequently, sufficient IP3 to activate the ion channel is released in the presynaptic neurone, so that less nenrotransmitter is released into the synaptic cleft (Figure 12.19). 

Nerve cells communicate by the release of chemicals (neurotransmitters) into the space between the cells (Figure 15.2). The neurotransmitter is typically stored in a small packet (synaptic vesicle) and then released in response to a signal that is transmitted down the cell axon. In the example in Figure 15.2, dopamine, an important neurotransmitter involved in movement disorders related to Parkinson s disease, is released into the gap (synaptic cleft) and reacts with specific receptors on the adjacent cell. This in turn causes a reaction in the adjacent cell. Dopamine in the gap can either be broken down or taken back up into the cell that released it and repackaged for future use. 

Once the electrical signal has arrived at a chemical synapse (see Fig 4.2) a cascade of events is triggered with the arrival of an electrical impulse (an action potential), a chemical compound known as a neurotransmitter is released from the presynaptic side into the synaptic cleft. The released neurotransmitter then reaches the membrane of the second cell (postsynaptic membrane) where it interacts with a macromolecule, a so-called receptor. It is this neurotransmitter receptor interaction that triggers another cascade of (chemical) reactions within the second cell and this ultimately leads to the generation of an electrical signal within this cell. This signal then is transferred along this second cell s axon towards another synapse. 

Synaptic cleft Gap of about 100 300 pm in diameter between two neurons. A neurotransmitter is released from the first neuron into the synaptic cleft and may interact with a receptor located on the membrane of the second neuron to trigger reactions leading to the propagation of information... 

Stimulants, such as amphetamine and methylphenidate, are potent releasers of DA, while cocaine also interferes with its reuptake, increasing DA concentrations at synaptic sites. All can produce paranoid reactions in some abusers. 

Schematic illustration of the interrelationships between glutamate and NO in synaptic function in the cetebellum. The presynaptic nerve terminal synthesizes, stores, and releases glutamate (G) as the neurotransmitter by exocytosis as illustrated. The glutamate diffu.ses across the synaptic cleft and interacts with postsynaptic NMDA recepti>rs ( ) that are coupled to calcium (Ca ) channels. Ca influx occurs and the free intracellular Ca complexes with calmtxlulin and activates NO synthase. NADPH is also required hir conversion, and the products of the reaction are NO plus L-citrulline. NO diffuses out of the piistsynaptic cell to interact with nearby target cells, one of which is the presynaptic neuron that released the glutamate in the first place. NO stimulates cytosolic guanylate cyclase and cyclic GMP (cGMP) formation presynaptically, hut the consequence of this pre.synaptic modification is unknown.

Acamprosate Antagonist of NMDA glutamate receptors May interfere with forms of synaptic plasticity that depend on NMDA receptors Treatment of alcoholism effective only in combination with counseling Allergic reactions, arrhythmia, and low or high blood pressure, headaches, insomnia, and impotence hallucinations, particularly in elderly patients... 

Tlie synaptic complex contains 240 bp of DNA and at least two resolvase dimers. All four DNA chains are cut to give eight ends. Four of these are bound to the serine side chains in phosphodiester linkage. In the second step the freed 3 -OH groups react with the bound ends of the other duplex via a transesterifica-tion reaction to form the recombinant chains. 

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