What's Up With The Stimulus-Receptor Signals In Our Body?

The idea of a lock and key mechanism was borne out of a need for security. We have valuables to safeguard. We have private issues that we don’t want to make public. We keep them locked up and hidden away. However, we do have keys to unlock those locks and gain access to our private stashes.

In the same way, a lot of the cells in our body communicate on a lock and key mechanism, which we can collectively term as “cell signalling”. Our cells have receptors on their surfaces, and specific biochemicals can bind to those receptors to signal them to do something.

For example, our cells possess insulin receptors. Insulin is produced by the beta cells in the pancreas when we consume food, and it then binds to the insulin receptor on the cell to signal the cell to take in glucose from the blood. In this situation, the presence of insulin unlocks the cell’s ability to take in glucose from the blood. Insulin stays in the insulin receptor for a specific period of time, which we call the residence time. After that period of residence, it disassociates from the receptor, which then reduces the cell’s ability to take in any more glucose from the blood.

Therefore, what we need to know is that we need the right number of keys to match with the right number of locks to produce a balanced signal. We'd be looking at achieving a dynamic equilibrium when everything is just about right, as I examined in The Delicate Balance Of A Steady State To Maintain A Healthy Body.

What happens when we have too much of a signal?

We can analyse the allergic reaction that hay fever causes. You know, that nasty thing when there are too many irritants in the air that we breathe, which then triggers off a release of histamines (excessively)...

These histamines can bind to histamine receptors located in different parts of the body. There are 4 major types of histamine receptors, which are denoted as H1-H4.

It is said in this article that:

H1 receptors mediate acute allergic responses; H2 receptors cause gastric acid secretion; H3 receptors mediate the postsynaptic effects of histamine released as a neurotransmitter; and H4 receptors are found predominantly on cells of hematopoietic origin such as dendritic cells, mast cells, eosinophils, monocytes, basophils, and T cells and are immunomodulatory.

Therefore, when there is too much of a histamine signal that can bind to the H1 receptors, the end result would be an overactive release of fluids in the form of tears and mucus - and that forms the basis of the allergic reaction right there.

And as I did mention in this article,

In an allergic reaction, what we do need to understand is the presence of mast cells. These cells contain many granules that are rich in histamines and interleukin cytokines. When allergens bind to the Immunoglobulin E (IgE) antibodies present on the surface of the mast cell, the mast cell releases its payload of histamines and interleukins to set off the allergic reaction.

However, even before that happens, we do see the effect of an increased activity in the IgE-producing B cells, which stem from an increased activity of the T helper 2 (Th2) cells. Certain interleukins that are released by the mast cell payload also do trigger the B cells to produce more IgE for a more pronounced allergic reaction the next time round. It’s a vicious positive feedback amplification loop that we’re looking at here.

It is the presence of this amplification loop that causes allergic reactions to worsen over time - they rarely improve for the better on their own, and that's because the dynamic equilibrium of the Th2 cellular activity has been significantly altered.

What happens when we have too little of a signal?

In Type 1 diabetes, for instance, the beta cell population is mistakenly diagnosed by the immune system to be a dangerous invader and is killed off by the immune system. The surviving beta cells do not have enough insulin production capacity and are underproducing insulin. When there are insufficient insulin keys to unlock all the insulin receptor locks, most cells will end up taking in less glucose than they are supposed to be taking in, leaving the leftover glucose to accumulate in the blood, which leads to diabetes over time.

Hence, having too much or too little of a signal is never any good. We need a balanced signal.

Some signals, fortunately, can be re-jigged more easily than others.

What do drugs do in the case of aberrant signals?

In the case of allergic reactions, it is said about the common antihistamine drugs that:

Most treatments of allergic conjunctivitis, including loratadine, desioratadine, and levocabastine, are aimed at H1 receptors; the exception is one drug, emedastine, which is aimed at H2 receptors.

What these drugs do is that they bind to the receptors as dummy keys to prevent the histamine molecules from binding to the receptors. While histamine will be able to unlock the function of the receptors, the dummy key drugs will not unlock receptor function. They remain there in the H1/H2 "keyholes" for the sole purpose of blocking the histamines from unlocking the H1/H2 functions.

In this way, one can use an antihistamine to address the symptoms of mucus hypersecretion.

1. But does the antihistamine address the problem of why the mast cells are providing such an adverse reaction to the presence of the allergen?

2. Does the antihistamine quell the release of the cytokines?

The answer, of course, is a resounding no.

If I were to pull an analogy here...

We'd be setting off a fire alarm right beside us, and the shrill tone of the alarm is getting on our nerves.

The antihistamine would function as a noise-cancelling headset.

Keep it on, and we can't hear the alarm. Take it away, and we'll get the full decibel blast of the alarm back in our face.

That's exactly what an antihistamine drug will do.

It quells the symptoms of the reaction, but it doesn't address the problem of the awry signalling at its roots.

But why would all these drugs be promoted or marketed?

Because it's all about the money, money, money...

A doctor's income is derived from the number of patients that come to them and from the drugs that they can prescribe.

If you had an allergic reaction, for instance, the doctor's first prescription would be for an antihistamine drug and perhaps a non-steroidal anti-inflammatory drug (NSAID).

These don't quell the issue at hand, but merely the symptoms.

When one is out of medications, but still has that lingering unsolved problem...

They'd have to go back to see the doctor again.

Repeat customers bring about recurring orders and a stable source of income for the doctor, don't they?

How many common chronic medical conditions are there that require recurring drug orders?

1. High cholesterol?

2. Type 1/2 diabetes?

3. Osteo/rheumatoid arthritis?

4. Atherosclerosis?

5. Hypertension?

There are too many of them to count.

As such, total pharmaceutical revenue worldwide exceeded US$1 trillion in 2014.

It's not rocket science.

Some of these problems can be addressed with proper nutrition and a massive lifestyle change, but even that isn't properly spelt out to the general public.

And the general public bears the brunt of it.

These diseases won't go away.

In fact, they will intensify as a result of extra stress brought about by increasing work demands/the COVID-19 pandemic/balancing out finances/relationship issues.

But there's always an option to break out of that vicious cycle.

Want to know more? Check this out:

Joel Yong, PhD, is a biochemical engineer/scientist, an educator and a writer. He has authored 1 ebook and co-authored 6 journal articles in internationally peer-reviewed scientific journals. His main focus is on finding out the fundamentals of biochemical mechanisms in the body that the doctors don’t educate the lay people about, and will then proceed to deconstruct them for your understanding — as an educator should. Do visit his website here to connect.