Human neural stem cells treated with 1 µM nicotine

Tobacco

Everyone knows cigarette smoking is dangerous and even deadly. We hear about the dangers from our doctors, teachers and parents, and we see warning labels on the packages “May cause cancer”. So why do people even smoke cigarettes? Why do approximately 3,000 teenagers begin smoking or using tobacco products each day? And why do over 45 million American adults still smoke, even though they may try quitting many times? There must be a reason why 31 million American adults want to quit smoking, but only about 5% are successful after one year.
 
The answer lies with a single molecule: nicotine. This natural ingredient is found in all tobacco products and can cause intense addiction. With repeated use, tobacco products can also lead to a host of deadly diseases such as cancers of the lung, mouth, and pancreas, emphysema, heart disease, and stroke.
 
What is nicotine and what are the effects on health?
One of the most abundant and highly addictive chemicals found in tobacco products is nicotine. Nicotine is found in high quantities in the tobacco leaves. Each tobacco product contains different amounts of nicotine, but on average, a typical cigarette contains about 10-15 mg, with the average smoker inhaling approximately 1-2 mg of nicotine.
 
At high doses, nicotine can be extremely poisonous. In fact, nicotine was previously used in insecticides to destroy insects, but its use as an insecticide was banned in the US in 2001 due to contamination of food products. Ingestion of high doses of nicotine causes vomiting, tremors, convulsions, and even death in a short amount of time. To put this in perspective, just one drop of pure nicotine can kill a person and 60 mg can be deadly. A small child or animal can become very sick or even die from eating just one cigarette left unattended. While ingestion of high doses of nicotine is not very common, the repeated use of products that deliver small amounts of nicotine can lead to a disease called addiction.
 
How does nicotine enter the body? Depending on the tobacco product used, nicotine can enter the body various ways. Cigarette smokers inhale nicotine from the smoke into their lungs. Smokeless tobacco users absorb nicotine through the skin and mucous membranes of the mouth. Nicotine can also enter through the mucous membranes in the nasal cavity (nose) if the oral form of dry snuff is used. Lastly, nicotine can be absorbed through the skin with use of products such as the nicotine patch. Regardless of the means of entry, nicotine quickly enters the bloodstream, where it can then be distributed throughout the body.
 
How does nicotine impact the brain?
One of the first areas to which nicotine travels is the brain. Regardless how nicotine enters the body (inhalation, mouth, nose, or skin), it will be absorbed into the bloodstream and reach the brain quickly. The fastest way to get nicotine to the brain is to inhale it—it only takes about 10 seconds for nicotine to reach the brain. This is because the blood from the lungs travels to the heart, which then pumps the blood through the arteries to all major organs, including the brain.
 
Once nicotine reaches the brain, it triggers a series of responses that alters the way cells in the brain communicate with each other. A brief review the function of the brain will help in understanding how nicotine causes its effects.

The brain is an amazing part of the body—it’s composed of billions of tiny cells called neurons, which communicate with each other to control all functions throughout the body. The brain regulates all aspects of life – pumping of the heart, breathing, walking, emotions, and memories. The brain is what differentiates humans from all other types of living species—humans are the only species to rationalize situations, have wild imaginations, and perform high level thoughts and tasks.

How does nicotine affect neurons and neurotransmitters?

One of the primary effects of nicotine is to alter the way that neurons (i.e., brain cells) communicate. Neurons communicate with each other through both electrical and chemical signals. Each neuron consists of a cell body (the main part of the neuron that contains the nucleus, or the cell’s control center), an axon, and many dendrites. The axon is one long extension from the cell body that carries electrical signals from one end of the neuron to the other end (referred to as the terminal). These signals travel extremely fast--up to hundreds of miles per second. Dendrites are shorter extensions that also branch off the cell body. Think of the dendrites as tree roots that branch out. The dendrites receive signals from other neurons in the form of chemicals.

Neurons communicate information to each other when they are in close contact. The connections between neurons are called synapses. On average, one neuron can form about 1,000 synapses with other neurons. With millions of neurons forming thousands of neural connections, it is estimated that the number of neuron-to-neuron connections in the brain exceeds the number of stars in our galaxy.

So how does the communication work at the synapse? First, an electrical impulse travels down the axon toward the terminal. Once there, the electrical signal triggers the release of chemicals called neurotransmitters from tiny sacs into the synaptic space outside the terminal. These chemicals actually carry the “messages” from one neuron to another. Once in the synaptic space, the neurotransmitter attaches to specific proteins called receptors on the dendrites of the neighboring neuron. There are thousands of receptors on the dendrites, with each type of receptor recognizing only a very specific neurotransmitter, similar to a lock and key. When the neurotransmitter binds (or attaches) to a specific receptor, the receptor will either increase or decrease the electrical activity of the neuron on which it resides.Let’s consider one of the major neurotransmitters in the brain called acetylcholine. Interestingly, nicotine mimics this neurotransmitter. Nicotine acts just like acetylcholine, but works even better. This is described below. Acetylcholine binds to receptors (“acetylcholine receptors”) that increase the electrical activity of neurons, resulting in more signals transmitted to neighboring neurons. Once acetylcholine has done its job, it is destroyed. New acetylcholine must be made by the cells to repeat the whole process.

As previously mentioned, nicotine mimics the effect of the neurotransmitter acetylcholine. When nicotine enters the brain, it can actually bind to the same receptors that bind acetylcholine. For this reason, the acetylcholine receptor is often referred to as a nicotinic receptor.

However, when one uses a tobacco product or another nicotinecontaining product, there is more nicotine available in the synaptic spaces compared to acetylcholine. The nicotine competes with acetylcholine to bind to the nicotinic receptors and it wins. Now, with more nicotinic receptors activated by nicotine, a more intense response is produced.

So while acetylcholine normally provides the just the right amount of alertness when it binds to its receptors, nicotine produces a much more intense response (increased alertness, pleasurable feelings) due to its higher concentrations at the acetylcholine receptors.

Nicotinic receptors are found in many other regions of the body besides the brain. Not surprisingly, nicotine acts in the body wherever nicotinic receptors are found, such as on the heart, blood vessels, and muscles. The widespread distribution of nicotinic receptors explains why nicotine will increase heart rate, blood pressure, and muscle contractions.

What happens with continued use of nicotine?

When one continues to use a product with nicotine in it, a strange thing happens. The number of nicotinic receptors—that is, acetylcholine receptors—increases on the neurons! With more receptors present, the person needs more acetylcholine binding to them to feel normal. But the neurons can only make so much acetylcholine. So what is the result? The person needs more nicotine to feel normal.

When the nicotine is not present, a person will often get symptoms such as headaches, tremors, shakiness, and an overall feeling of irritability and frustration. To get rid of these “withdrawal” symptoms, the user will smoke another cigarette or use another tobacco product and begin to feel much better. The presence of withdrawal symptoms is typical of dependence and it almost always precedes addiction.

In addition, the increased nicotinic receptors can also explain tolerance, or the need to use more of the product containing nicotine to get the original effect.

Can receptors recover from nicotine exposure?

The good news is that the increase in receptor number is probably not permanent. Once one stops using a product containing nicotine, the number of receptors will return to normal pre-nicotine levels—although this could take more than a year. However, immediately after stopping smoking for example, many users experience unpleasant withdrawal symptoms because the brain now has an excess of nicotinic receptors, which are unoccupied. The long process for the brain to recover to normal is one reason why many people who try to quit using nicotine products can’t get past the first year (or even week!) nicotine-free.

 

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