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What is the difference between neurotransmitters acting as neurotransmitters and hormones?

What is the difference between neurotransmitters acting as neurotransmitters and hormones?


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My main confusion is what differentiates the action of a transmitter substance as a neurotransmitter and as a hormone. For example, when norepinephrine is being talked about as transmitter substance that modulates brain responsiveness and information processing, it's a neurotransmitter. But when norepinephrine is involved in the functions of the autonomic nervous system (ANS), does it work as a hormone or a neurotransmitter?

Quoting from Physiology of Behavior, by N. Carlson, 2013 edition:

"Neurons in the central nervous system contain a1- and a2-adrenergic receptors and b1- and b2-adrenergic receptors. All four kinds of receptors are also found in various organs of the body besides the brain and are responsible for the effects of epinephrine and norepinephrine when they act as hormones outside the central nervous system."

So does that mean that whenever norepinephrine works outside the CNS, it works as a hormone?


This figure from Campbell (2011), chapter 45, is very didactic and may clarify this nomenclature for you.

The processes of interest here are a, d and e:

The definition of hormone (in animals) is quite simple: a signaling molecule released in the bloodstream. That's the process a in the figure.

On the other hand, a neurotransmitter is released in the synapse, acting locally. That's the process d in the figure.

However, some nerve cells release their signaling molecule in the bloodstream (process e in the figure). Unlike the synaptic signaling, this molecule can act on a target cell at great distance.

So, despite the fact that we're talking about the very same molecule (norepinephrine in your example), in that last process this molecule is technically speaking a hormone, not a neurotransmitter anymore.


Source: Reece, J., Reece, J. and Campbell, N. (2011). Campbell biology. Boston: Pearson Learning Solutions.


Right. It's nomenclature to differentiate actions and release in the CNS (neuronal) versus outside (endocrine in this case). A neurotransmitter will act locally to it's release site typically from a neuronal synapse, while hormones tend to be released into the bloodstream and can act much further away as well as at a different time scale.

Source from textbook: Principles of Neural Science (Fourth Edition), Kandel et al. 2000, McGraw-Hill Medical ISBN 10: 0071120009


Difference Between Neurotransmitters and Hormones

The key difference between neurotransmitters and hormones is that neurotransmitters are the chemical messengers used by the nervous system to transmit nerve impulse across the synapses while hormones are the chemical messengers used by the endocrine system to stimulate or communicate with specific targets cells.

Nervous system and endocrine system are very important organ systems in our body that regulate various activities. Both systems are dependent on the release of special chemicals either as neurotransmitters or as hormones respectively. These neurotransmitters and hormones act as chemical messengers and facilitate the nerve impulse transmission and the regulation of physiological activities in our body.

CONTENTS


Dopamine vs. serotonin: the similarities

As previously mentioned, both dopamine and serotonin are neurotransmitters. More importantly, they’re in a special class of neurotransmitters known as neural modulators. “What that means is that these chemicals can communicate with both nearby neurons, as well as impact neurons far away from the site of release,” says Dr. Wise. “Serotonin and dopamine&mdashas neuromodulators&mdashhave a further range of action when compared to regular neurotransmitters. And this also means that they can have much longer lasting effects than the regular neurotransmitters.”


Types of neurotransmitters

1. Dopamine

Dopamine is one of the most popular types of neurotransmitters, and it is directly related to the feeling of well – being, pleasure and relaxation. Dopamine originates in an area of ​​the brain that is known as a black substance and fulfills a very important function in the control of our musculoskeletal system, so it coordinates movement.

Being also essential for the proper functioning of the central nervous system, it performs a role that is key in human behavior, which is why it is called the neurotransmitter of happiness.

Another important function with which this type of neurotransmitter fulfills is that by producing a depolarizing effect in neurons, there is excellent communication between them, which favors learning, attention, and memory.

2. Serotonin

This type of neurotransmitter also serves as a hormone. It is located in different sections of the central nervous system and its main function is to regulate the activity of other neurotransmitters.

Serotonin is directly involved in various processes such as digestion, regulation of anxiety and stress levels, body thermal regulation, sleep, appetite, mood, and sexual desire.

3. Noradrenaline

This type of neurotransmitter is also known as the stress hormone and, like serotonin, it serves a double function (neurotransmitter and hormone). Norepinephrine is responsible for activating the sympathetic nervous system and is associated with heart rate and certain processes responsible for attention and the generation of a stress response.

4. Adrenaline

This neurotransmitter that is extremely similar to norepinephrine, is responsible for developing survival mechanisms when we are in real or even imaginary danger. It also meets some physiological reactions, such as breathing and blood pressure.

5. Glutamate

It is the main excitatory neurotransmitter of the central nervous system. Glutamate is related to the GABA neurotransmitter and has a very important role in memory processes and their recovery, among other mental processes.

6. Gamma-aminobutyric acid (GABA)

This type of neurotransmitter is responsible for stopping or inhibiting the action of some excitatory neurotransmitters. The goal of doing so is to prevent us from having certain reactions of exaggerated fear and anxiety and that only causes us discomfort.

7. Acetylcholine

This neurotransmitter is found in different areas of the central nervous system, at synapses of glands and in muscles. It is responsible for stimulating muscles, activating motor neurons, promotes memory and association processes, as well as the transition from sleep to wakefulness.


What is a Neurohormone?

A neurohormone is a chemical messenger that is released by neuroendocrine cells. Neuroendocrine cells are cells that receive an input from neurons like neurotransmitters, and in response output or release messenger molecules (a.k.a. hormones) into the blood stream.

By releasing the hormones into the blood stream, neurohormones can exert its effect on very distant peripheral targets. Neurohormones differ from neuromodulator in the extent of their actions.

So an example of neuroendocrine cell is the cells of the adrenal medulla, which is the innermost part of the adrenal gland. The adrenal medulla releases adrenaline into the blood stream in response to stimulation by the sympathetic preganglionic neurons, which are neurons from the autonomic nervous system.

You should also note that hormones last up to 10 times longer than neurotransmitters


Hormones and Chemicals Linked with our Emotion

Emotions are very complex and have different meanings to different people, but essentially, emotions are a conscious experience that are categorized by states of mind, external and internal reactions, and expressions.

There are many different emotions, including affection, anger, angst, anguish, annoyance, anxiety, apathy, arousal, awe, boredom, confidence, contempt, contentment, courage, curiosity, depression, desire, despair, disappointment, disgust, distrust, dread, ecstasy, embarrassment, envy, euphoria, excitement, fear, frustration, gratitude, grief, guilt, happiness, hatred, hope, horror, hostility, hurt, hysteria, indifference, interest, jealousy, joy, loathing, loneliness, love, lust, outrage, panic, passion, pity, pleasure, pride, rage, regret, relief, remorse, sadness, satisfaction, self-confidence, shame, shock, shyness, sorrow, suffering, surprise, terror, trust, wonder, worry, zeal, and zest.

Emotions are not really made out of anything, but how we feel emotions can be described. Emotions come from the arousal of the nervous system. Millions of chemical reactions take place in the brain at any given time. Chemical reactions occur because of synapses. Synapses are parts of the nervous system, and it is through these that neurons are able to transmit messages using neurotransmitters.

Emotions are typically measured in physiological responses, such as a pounding heart, sweating, blood rushing to the face, and the release of adrenaline. Expression is also a major part of emotions. Expression is associated with parts of the nervous system such as the motor cortex, limbic system, and the brain stem. The parts of the nervous system that affect emotion the most are the frontal lobes and the amygdala. The frontal cortex is usually associated with feelings of happiness and pleasure. The amygdala is usually associated with feelings of anger, fear, and sadness.

We experience a variety of emotions throughout the day. Mostly, these emotions are transient in nature. But, when these emotions become intensely negative or are unremitting they can dramatically affect our biochemistry and behaviour.Certain brain areas and the presence of levels of different chemicals in your brain controls emotions. For example, if we are in danger, our brain releases stress hormones that can initiate fight or flight reactions by flooding certain regions with the neurotransmitter epinephrine (adrenaline). When the danger subsides, our brain inhibits the stress response by sending out a calming signal in the form of chemicals.

Hormones and chemicals keep the body working normally. Listed are a few of them and how their balance affect the way our moods, emotions and stresses are triggered.

    Oestrogen – Female Reproduction and Positive Mood Hormone


Similarities Between Neurotransmitter and Neuromodulator

  • Neurotransmitter and neuromodulator are two types of chemical messengers released by the nervous system.
  • The terminus of the presynaptic neuron stores them in vesicles and releases them into the synapses.
  • They transmit neuron impulses through the synapse.
  • Moreover, they bind to specific receptors on the post-synaptic neuron or effector cells.
  • And, their effect can be either excitatory or inhibitory.

Drugs That Influence Neurotransmitters

Perhaps the greatest practical application for the discovery and detailed understanding of how neurotransmitters function has been the development of drugs that impact chemical transmission. These drugs are capable of changing the effects of neurotransmitters, which can alleviate the symptoms of some diseases.

  • Agonists vs Antagonists: Some drugs are known as agonists and function by increasing the effects of specific neurotransmitters. Other drugs and referred to as antagonists and act to block the effects of neurotransmission.  
  • Direct vs Indirect Effects: These neuro-acting drugs can be further broken down based on whether they have a direct or indirect effect. Those that have a direct effect work by mimicking the neurotransmitters because they are very similar in chemical structure. Those that have an indirect impact work by acting on the synaptic receptors.

Drugs that can influence neurotransmission include medications used to treat illness including depression and anxiety, such as SSRIs, tricyclic antidepressants, and benzodiazepines.

Illicit drugs such as heroin, cocaine, and marijuana also have an effect on neurotransmission. Heroin acts as a direct-acting agonist, mimicking the brain's natural opioids enough to stimulate their associated receptors. Cocaine is an example of an indirect-acting drug that influences the transmission of dopamine.  


Hormones

Hormones are substances that are secreted (or released) by cells that act to regulate the activity of other cells in the body. As a result, many activities in the human body are regulated by hormones. For example, reacting to fear, developing male or female characteristics, and growing taller are all regulated by hormones. Hormones are important to keep your body functioning.

There are four major functions identified with hormones. Hormones regulate growth, development, behavior, and reproduction. Hormones coordinate the production, use and storage of energy. Hormones are involved in maintaining nutrition, metabolism, excretion, and water and salt balance. And finally, hormones react to stimuli from outside the body.

Hormones act as chemical messengers that carry instructions to other cells to change their activity. The heart beats faster as hormones carry instructions to the cells of the heart telling it to increase the heartbeat. It was once believed that hormones had to travel through the bloodstream, but scientists know today that that is not true. Some hormones act directly on adjacent cells without traveling through the blood.

The message that a hormone carries is determined by both the hormone itself and the cell it is carrying the message to. A hormone can instruct a cell to produce an enzyme or a specific protein. Simply put, hormones can instruct a muscle cell to relax and a nerve cell to fire.

Each hormone is specific to the cell it is traveling to. Each hormone acts like a key that opens a lock on or inside the cell. A hormone can only act on cells with the right lock.

Endocrine glands are important organs in the human body that hormones are secreted from. All of the endocrine glands together make up the endocrine system. The endocrine system coordinates the body's entire source of hormones.

There are several other organs that contain cells that secrete hormones. These organs include the brain, stomach, small intestine, kidney, liver, and heart.

The endocrine system and the nervous system interact to coordinate the overall activity of the body., and hormones play an important role.

The chemical messengers for the nervous system are known as neurotransmitters while the chemical messengers for the endocrine system are known as hormones. There are some nerve cells that are able to secrete hormones. For example, epinephrine is both a neurotransmitter and a hormone.

Hormones are normally a slower-acting and longer-lived messenger whereas the neurotransmitters are usually fast-acting and short-lived. The effect of a hormone can last for days, weeks, or even years.

After a hormone is released from the cell in which it is made, they bind and act on target cells. A target cell is a specific cell a hormone binds to and carries the message. If the hormone was not specific, all the cells in the body would react to a hormone resulting in uncoordinated activities.

Finally, there are two main hormone classifications. They are either amino-acid-based hormones or they are steroid-based hormones. Amino-acid-based hormones are water soluble and made up of amino acids. Steroid-based hormones are lipid hormones made from cholesterol and are fat soluble.

Since the human body makes more than 40 hormones, it is important that the release of them is regulated regardless of which hormone is being produced.


Difference Between Adrenaline and Noradrenaline

Definition

Adrenaline refers to a hormone secreted by the adrenal glands, increasing rates of blood circulation, breathing, and carbohydrate metabolism and prepares muscles for exertion while noradrenaline refers to a hormone released by the adrenal medulla and by the sympathetic nerves and functions as a neurotransmitter it is also used as a drug to raise blood pressure. Thus, this is the main difference between adrenaline and noradrenaline.

Production

Moreover, adrenaline is exclusively produced by the medulla of the adrenal gland while noradrenaline is produced by both the medulla of the adrenal gland and the sympathetic nervous system.

Biosynthesis

Another difference between adrenaline and noradrenaline is that the adrenaline is synthesized from noradrenaline while the noradrenaline is synthesized from dopamine.

Chemical Structure

Furthermore, adrenaline contains a methyl group attached to its nitrogen while noradrenaline contains hydrogens attached to nitrogen.

Receptor Activation

Receptor activation is another difference between adrenaline and noradrenaline. Adrenaline activates both alpha and beta adrenergic receptors while noradrenaline only activates alpha adrenergic receptors.

Effect

The four effects of adrenaline are the increase in the heart rate and contractility, relaxation of breathing tubes, increase in blood pressure by vasoconstriction, and the increase of the blood sugar levels while the main effect of noradrenaline is vasoconstriction. Hence, this is another difference between adrenaline and noradrenaline.

Conclusion

Adrenaline is the main hormone secreted by the medulla of the adrenal gland. It activates both alpha and beta-adrenergic receptors. The main function of adrenaline is to increase the metabolism of the body by increasing the blood flow, breathing rate, and glucose availability. On the other hand, noradrenaline is a neurotransmitter, which activates only alpha adrenergic receptors. Therefore, the main effect of this substance is to increase the blood pressure via vasoconstriction. Hence, the main difference between adrenaline and noradrenaline is their effect while preparing the body to stressful situations.

Reference:

1. “Norepinephrine vs Epinephrine: What’s the Difference?” Drugs.com, Drugs.com, Available Here

Image Courtesy:

1. “Adrenaline” By Harbin – Own work (Public Domain) via Commons Wikimedia
2. “Synapse noradrenergique1” By Pancrat – Own work (CC BY-SA 3.0) via Commons Wikimedia

About the Author: Lakna

Lakna, a graduate in Molecular Biology & Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things


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