Nervous system transmitter-receptor interaction

There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of biogenic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Amino acid neurotransmitters are glutamic and aspartic acids that excite postsynaptic membrane receptors of several neurons as well as y-aminobutyric acid (GABA) and glycine, which are inhibitory neurotransmitters. Endorphins, enkephalins, and substance P are considered peptidergic transmitters. There are many compounds that imitate the action of these neurotransmitters. 

Intercellular communication in the nervous system is typically mediated through synaptic transmission via the release of neurotransmitters and their subsequent binding to specific receptors. The transmitter-receptor interaction then elicits changes in ion channel permeability and/or second messenger formation in the innervated cell. Neurotransmitters can also interact with receptors located on the presynaptic terminal (either autoreceptors, which are activated by the same transmitter, or heteroreceptors, which are activated by a different transmitter released by a different neuron) to regulate the presynaptic function, often by influencing neurotransmitter release. Termination of synaptic neurotransmission depends upon the removal of neurotransmitter molecules from the synaptic cleft by either enzymatic degradation or by reuptake into the presynaptic terminal. 

In the sympathetic part of the peripheral autonomic nervous system the simation is less complicated since only the sympathetically innervated visceral organs have receptors sensitive to the transmitter of the postganglionic sympathetic neuron noradrenaline. However, the noradrenaline sensitive receptors, which all belong to the G-protein coupled receptor superfamily, can be subdivided in at least three subtypes ai-, a - and jSi-adrenoceptors. These receptors are to a similar extent sensitive to adrenaline, a humoral transmitter which is released under sympathetic control from the adrenal medulla. Adrenaline, in contrast to noradrenaline has affinity to a forth type, the /32-adrenoceptor. In general drug interacting with the autonomous nervous system can be subdivided according to their mechanism of action. 

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on postsynaptic neuronal membranes of both the sympathetic and parasympathetic nervous systems. 

The individual unit of the nervous system is the neuron, a specialized cell that both receives and transmits information. The nervous system contains more than 100 billion neurons and is a major user of metabolic energy in the human body. It is also a region particularly susceptible to injury from toxic chemicals, lack of oxygen, and other assaults. Depending on the nervous region in which they reside, neurons may have different anatomical features and may use different chemical transmitters. Neurons communicate with each other and with their end organs by these chemical signals, which are released from the nerve terminal and interact with specific receptors on adjacent neurons or cells. 

There are three main types of opioid receptor OP3 (p), OP2 (k), and OPi (5) receptors. They are mainly found within the central nervous system but also in the periphery. Subtypes of each have been identified. Opioids interact with these receptors to produce their effects, primarily by exerting presynaptic inhibition, which results in reduced release of excitatory transmitters. It is thought that analgesia is primarily mediated via activation of OP3... 

One of the corner-stones of life is recognition. This phenomenon occurs on a macroscopic level as well as on a microscopic one. For example, the ability to recognize a familiar face is practical in our everyday life and the recognition of a transmitter substance by its receptor is essential for the function of the nervous system. Molecular recognition is the creation of a complex between a host molecule and a guest molecule and often involves non-covalent interactions such as hydrogen bonds, hydrophobic interactions, metal coordination, van der Waals interactions and ionic interactions. 

When a nerve impulse arrives at a synapse, it causes the release of a minute amoimt of a chemical substance called a neurotransmitter (or synaptic transmitter) which is a localized hormone. This substance diffuses across the gap and, on reaching the far side, it interacts with receptors on the post-synaptic membrane of a muscle or nerve cell. As soon as it has acted, the neurotransmitter is removed from the synaptic cleft, either by reabsorption into the pre-synaptic store (noradrenaline) or by enzymatic destruction (acetylcholine). The synapse is thus rapidly restored to its resting state, ready for another impulse. The most familiar transmitters of the peripheral nervous system are acetylcholine (7.4) and noradrenaline (7.5). It has been suggested that ATP is the neurotransmitter released by the non-adrenergic inhibitory innervation of the gut (Burnstock et aL 1970). In many invertebrates, such as crustaceans, molluscs, and flat worms, dopamine and 5-hydroxytryptophan have been observed playing the roles that belong to acetylcholine and noradrenaline in mammals. 

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