Neurotransmitters, part two: adenosine, acetylcholine, glutamate and gamma-aminobutyric acid
The first part of the story about neurotransmitters Atlas was dedicated to youth dopamine, norepinephrine and serotonin. In the second post, we will focus on less well-known mediators that perform important invisible work: they stimulate and inhibit other neurotransmitters, help us learn and memorize.
This is the first neurotransmitter that scientists have discovered. It is responsible for the transmission of impulses by motor neurons - and therefore, for all human movements. In the central nervous system, the neurotransmitter takes on stabilizing functions: it removes the brain from a state of rest when it is necessary to act, and vice versa, it slows down the transmission of impulses when it is necessary to concentrate. Two types of receptors help him in this - accelerating nicotine and inhibiting muscarinic.
Acetylcholine plays an important role in the process of learning and memory formation. This requires both the ability to focus attention (and inhibit the transmission of distracting pulses) and the ability to switch from one object to another (and accelerate the reaction). The active work of the brain, for example, in preparing for the exam or annual report, leads to an increase in the level of acetylcholine. If the brain is inactive for a long time, a special enzyme, acetylcholinesterase, destroys the mediator, and the action of acetylcholine weakens. Ideal for learning, acetylcholine will be a bad helper in stressful situations: it is a mediator of reflection, but not decisive action.
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An excess of acetylcholine in the body causes a spasm of all muscles, convulsions and respiratory arrest - some nerve gases are calculated on this effect. Lack of acetylcholine leads to the development of Alzheimer's disease and other types of senile dementia. As a maintenance therapy, patients are prescribed a drug that blocks the destruction of acetylcholine, an acetylcholinesterase inhibitor.
The CHRNA3 gene encodes the nicotinic acetylcholine receptor, which can be affected by nicotine. At the first stage, the substance acts on the sympathetic system of the body, which is responsible for the spasm of smooth muscles and vascular contraction. Therefore, in beginning smokers, cigarettes cause nausea and pallor of the skin rather than delight. But over time, nicotine reaches brain cells and activates acetylcholine receptors. Since both nicotine and acetylcholine are doing this at the same time, the brain tries to correct the “double feed”, and after a while the neurons of the brain reduce the normal production of acetylcholine. From this point on, nicotine will be needed by the smoker on every occasion - in the morning to cheer up, after the meeting, on the contrary, to calm down, after lunch - in order to at least think about the eternal.
Polymorphism of the CHRNA3 gene affects the rate of nicotine addiction formation and, as a result, the risk of lung cancer caused by smoking.
All chemical reactions in the body require energy. The adenine molecule with several phosphoric acid bases is used as a currency in this process. Immediately after the "salary" on your card will be "three hundred rubles" - a molecule of adenosine three phosphate with three phosphoric acid residues. Each transaction takes a hundred rubles, respectively, after the first “purchase” only two hundred rubles will remain on the account (adenosine di phosphate), after the second - a hundred rubles (adenosine mono phosphate), after the third - zero rubles.
The denomination in zero rubles is adenosine. As a neurotransmitter, he is responsible for feeling tired and falling asleep. During sleep, bills with zero-zero rubles are drawn three times, adenosine is transformed into adenosine triphosphate, and we are ready to return to work with new forces.
There is a way to trick the "banking system": block the adenosine receptors and go on credit. This is exactly what caffeine does - it allows you to ignore fatigue and continue working. At the same time, it does not bring real energy, but only allows you to spend money, as if you still have three hundred rubles. As with any loan, you have to pay for the overspending - more fatigue, slow attention, addiction. However, caffeine-containing coffee, tea and chocolate are the most popular stimulant in the world.
There are a total of four types of adenosine receptors that are activated and blocked by adenosine. The ADORA2A gene encodes adenosine receptors of the second type, which are involved in the activation of anti-inflammatory processes, the formation of the immune response, the regulation of pain and sleep. The rate of the body’s response to injury and trauma depends on the work of this receptor.
Glutamic acid in the form of glutamate is a food-grade amino acid found in foods of animal origin. Taste receptors perceive glutamate as an indicator of protein foods - which means nutritious and healthy - and leave a note that was delicious, and must be repeated. In the twentieth century, Japanese scientists discovered the principle of perception of this taste (they called it “umami” - delicious), and over time, monosodium glutamate became a popular food additive. Thanks to him, it is sometimes difficult to resist the temptation to eat noodles noodles. As a dietary supplement, glutamate does not directly affect the work of neurons, so its “overdose” will in the worst case be a headache.
Glutamate is not only a food amino acid, but also an important neurotransmitter, whose receptors are in 40% of brain neurons. It does not have its own "semantic load", but only accelerates the signal transmission by other receptors - dopamine, noradrenaline, serotonin, etc. This function allows glutamate to form synaptic plasticity - the ability of synapses to regulate their activity depending on the reaction of postsynaptic receptors. This mechanism underlies the process of learning and working memory.
Decreased glutamate activity leads to lethargy and apathy. Surplus - to the "overvoltage" of nerve cells and even their death, as if the electrical network was given a greater load than it can withstand. "Burnout" of neurons - excitotoxicity - is observed after attacks of epilepsy and in neurodegenerative diseases.
Two groups of genes encode glutamate transporter proteins. The genes of the EAAT group are responsible for sodium-dependent proteins - the ones that are involved in the memorization process. Mutations in the genes of this group increase the risk of stroke, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis. Mutations in the genes of vesicular protein transporters of the VGLUT group are associated with the risk of schizophrenia.
Each yin has its own yang, and glutamate has its eternal adversary, with which it is nevertheless inextricably linked. This is the main inhibitory neurotransmitter - gamma-aminobutyric acid (GABA or GABA). Like glutamate, GABA does not introduce new colors into the spectrum of brain activity, but only regulates the activity of other neurons. Like glutamate, GABA has covered about 40% of brain neurons with its receptor network. Both glutamate and GABA are synthesized from glutamic acid and are essentially a continuation of each other.
To describe the effect of GABA, the saying “go quieter - you will continue” is ideal: the inhibitory effect of the mediator allows you to concentrate better. GABA reduces the activity of a variety of neurons, including those associated with a sense of fear or anxiety and distracting from the main task. High concentration of GABA provides calm and composure. A decrease in GABA concentration and an imbalance in eternal resistance with glutamate leads to attention deficit disorder (ADHD). To increase the level of GABA, walks, yoga, meditation are well suited, and most stimulants are suitable for reducing.
Gamma-aminobutyric acid has two types of receptors - GABA-A rapid response and GABA-B slower action. The GABRG2 gene encodes a GABA-A receptor protein, which dramatically reduces the rate of transmission of impulses in the brain. Mutations in the gene are associated with epilepsy and febrile seizures that can occur at high temperatures.
If dopamine, serotonin and norepinephrine - Hollywood actors of the large neural film industry, the heroes of the second part of the story about neurotransmitters are more likely to work behind the scenes. But without their imperceptible contribution a great movie would be completely different.
In the next part , Atlas will talk about peptides and opioids - this topic requires a separate discussion.
PS Beginning and continuation .
Acetylcholine
This is the first neurotransmitter that scientists have discovered. It is responsible for the transmission of impulses by motor neurons - and therefore, for all human movements. In the central nervous system, the neurotransmitter takes on stabilizing functions: it removes the brain from a state of rest when it is necessary to act, and vice versa, it slows down the transmission of impulses when it is necessary to concentrate. Two types of receptors help him in this - accelerating nicotine and inhibiting muscarinic.
Acetylcholine plays an important role in the process of learning and memory formation. This requires both the ability to focus attention (and inhibit the transmission of distracting pulses) and the ability to switch from one object to another (and accelerate the reaction). The active work of the brain, for example, in preparing for the exam or annual report, leads to an increase in the level of acetylcholine. If the brain is inactive for a long time, a special enzyme, acetylcholinesterase, destroys the mediator, and the action of acetylcholine weakens. Ideal for learning, acetylcholine will be a bad helper in stressful situations: it is a mediator of reflection, but not decisive action.
')
An excess of acetylcholine in the body causes a spasm of all muscles, convulsions and respiratory arrest - some nerve gases are calculated on this effect. Lack of acetylcholine leads to the development of Alzheimer's disease and other types of senile dementia. As a maintenance therapy, patients are prescribed a drug that blocks the destruction of acetylcholine, an acetylcholinesterase inhibitor.
The CHRNA3 gene encodes the nicotinic acetylcholine receptor, which can be affected by nicotine. At the first stage, the substance acts on the sympathetic system of the body, which is responsible for the spasm of smooth muscles and vascular contraction. Therefore, in beginning smokers, cigarettes cause nausea and pallor of the skin rather than delight. But over time, nicotine reaches brain cells and activates acetylcholine receptors. Since both nicotine and acetylcholine are doing this at the same time, the brain tries to correct the “double feed”, and after a while the neurons of the brain reduce the normal production of acetylcholine. From this point on, nicotine will be needed by the smoker on every occasion - in the morning to cheer up, after the meeting, on the contrary, to calm down, after lunch - in order to at least think about the eternal.
Polymorphism of the CHRNA3 gene affects the rate of nicotine addiction formation and, as a result, the risk of lung cancer caused by smoking.
Adenosine
All chemical reactions in the body require energy. The adenine molecule with several phosphoric acid bases is used as a currency in this process. Immediately after the "salary" on your card will be "three hundred rubles" - a molecule of adenosine three phosphate with three phosphoric acid residues. Each transaction takes a hundred rubles, respectively, after the first “purchase” only two hundred rubles will remain on the account (adenosine di phosphate), after the second - a hundred rubles (adenosine mono phosphate), after the third - zero rubles.
The denomination in zero rubles is adenosine. As a neurotransmitter, he is responsible for feeling tired and falling asleep. During sleep, bills with zero-zero rubles are drawn three times, adenosine is transformed into adenosine triphosphate, and we are ready to return to work with new forces.
There is a way to trick the "banking system": block the adenosine receptors and go on credit. This is exactly what caffeine does - it allows you to ignore fatigue and continue working. At the same time, it does not bring real energy, but only allows you to spend money, as if you still have three hundred rubles. As with any loan, you have to pay for the overspending - more fatigue, slow attention, addiction. However, caffeine-containing coffee, tea and chocolate are the most popular stimulant in the world.
There are a total of four types of adenosine receptors that are activated and blocked by adenosine. The ADORA2A gene encodes adenosine receptors of the second type, which are involved in the activation of anti-inflammatory processes, the formation of the immune response, the regulation of pain and sleep. The rate of the body’s response to injury and trauma depends on the work of this receptor.
Glutamate
Glutamic acid in the form of glutamate is a food-grade amino acid found in foods of animal origin. Taste receptors perceive glutamate as an indicator of protein foods - which means nutritious and healthy - and leave a note that was delicious, and must be repeated. In the twentieth century, Japanese scientists discovered the principle of perception of this taste (they called it “umami” - delicious), and over time, monosodium glutamate became a popular food additive. Thanks to him, it is sometimes difficult to resist the temptation to eat noodles noodles. As a dietary supplement, glutamate does not directly affect the work of neurons, so its “overdose” will in the worst case be a headache.
Glutamate is not only a food amino acid, but also an important neurotransmitter, whose receptors are in 40% of brain neurons. It does not have its own "semantic load", but only accelerates the signal transmission by other receptors - dopamine, noradrenaline, serotonin, etc. This function allows glutamate to form synaptic plasticity - the ability of synapses to regulate their activity depending on the reaction of postsynaptic receptors. This mechanism underlies the process of learning and working memory.
Decreased glutamate activity leads to lethargy and apathy. Surplus - to the "overvoltage" of nerve cells and even their death, as if the electrical network was given a greater load than it can withstand. "Burnout" of neurons - excitotoxicity - is observed after attacks of epilepsy and in neurodegenerative diseases.
Two groups of genes encode glutamate transporter proteins. The genes of the EAAT group are responsible for sodium-dependent proteins - the ones that are involved in the memorization process. Mutations in the genes of this group increase the risk of stroke, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis. Mutations in the genes of vesicular protein transporters of the VGLUT group are associated with the risk of schizophrenia.
Gamma Aminobutyric Acid
Each yin has its own yang, and glutamate has its eternal adversary, with which it is nevertheless inextricably linked. This is the main inhibitory neurotransmitter - gamma-aminobutyric acid (GABA or GABA). Like glutamate, GABA does not introduce new colors into the spectrum of brain activity, but only regulates the activity of other neurons. Like glutamate, GABA has covered about 40% of brain neurons with its receptor network. Both glutamate and GABA are synthesized from glutamic acid and are essentially a continuation of each other.
To describe the effect of GABA, the saying “go quieter - you will continue” is ideal: the inhibitory effect of the mediator allows you to concentrate better. GABA reduces the activity of a variety of neurons, including those associated with a sense of fear or anxiety and distracting from the main task. High concentration of GABA provides calm and composure. A decrease in GABA concentration and an imbalance in eternal resistance with glutamate leads to attention deficit disorder (ADHD). To increase the level of GABA, walks, yoga, meditation are well suited, and most stimulants are suitable for reducing.
Gamma-aminobutyric acid has two types of receptors - GABA-A rapid response and GABA-B slower action. The GABRG2 gene encodes a GABA-A receptor protein, which dramatically reduces the rate of transmission of impulses in the brain. Mutations in the gene are associated with epilepsy and febrile seizures that can occur at high temperatures.
If dopamine, serotonin and norepinephrine - Hollywood actors of the large neural film industry, the heroes of the second part of the story about neurotransmitters are more likely to work behind the scenes. But without their imperceptible contribution a great movie would be completely different.
In the next part , Atlas will talk about peptides and opioids - this topic requires a separate discussion.
PS Beginning and continuation .
Source: https://habr.com/ru/post/398085/
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