Earlier, we referred to the most effective (and expensive) medication for migraine – Imitrex. There are several other medications similar to its mode of action: All of them are analogues of serotonin, and, being injected or taken as a pill, they suppress the levels of serotonin in the body. Like treats like? Yes.
Basic science knows that histamine is superior to serotonin in its effects. In science, there is a term – autacoid. It consists of two Latin roots – auta (auto) – self, and coid – remedy. Both histamine and serotonin belong to this group. We have just mentioned the use of serotonin analogues in fighting its high levels. Can histamine analogues be used in a similar way as long as it is also an autacoid? Do they exist? Could we use the analogue of histamine in the way we use serotonin and solve the problem. Since histamine regulates the level of serotonin along with other mediators, by normalizing the levels of the inferior serotonin, we achieve only a temporary relief, while the correction of the levels of the superior histamine might give radical results. We are only making deductions and need to search for the proof in medical literature. We cannot rely on the opinion of a doctor or a group of scientists; we need a textbook or scientific sources accepted by today’s medicine. They do exist. For that, we need to see how substances work in organs and tissues.
Anything that finds a response in the body has a special receptor or a even several kinds of receptors. Like small cellular antennae, these receptors react to a specific signal. There are receptors responding light, sounds, colors, and substances. The role of receptors is to receive the signal and pass its message inside the cell, to its cytoplasm, which is the laboratory producing different substances in response to the message received. Thus, every signal received by the cellular antennae changes the body’s chemistry. The healthier the receptors, the clearer their message to the lab. Thus, inefficient or underdeveloped receptors can be compared to a broken TV antenna with the resultant poor image on the screen. There are several receptors marked by the letter S that respond to serotonin. They react both to the serotonin produced inside the body and to the synthetic version injected or swallowed as a drug. There are four kinds of histamine receptors marked by letter H, and they react to histamine. Let’s see what they do in the body. It is of great importance especially in view of histamine production by all cells of the body. How important is it for them to be healthy and active and properly receive and pass along histamine messages?
H1 receptor is most active in smooth muscles and in vessels. It is also extremely important for the activity of natural killers – the cells that fight cancer. This receptor is the cause of profound histamine production by the cells. In other words, they respond to the histamine in the intracellular space. The cells produce it among other substances, as is the task of nature. It leaks through the pores in the cellular membrane, and H1 receptors feel it, get active and report back to the cell - produce more. The process goes on all the time. Those tissues that have more receptors produce more histamine. The brain is such tissue. When the amount of histamine is normal, our brain functions normally. Histamine excess gives us a headache. Any vascular headache, not only migraine, depend on histamine leakage, and hence, on the work of H1 receptor. The question is: why is H1 is too industrious in some people and not in all of us? Maybe other receptors can help us in sorting this out?
H2 and H3 receptors moderate the activity of H1 receptor. If the function of H1 receptor is to make cells produce histamine incessently, H2 and H3 receptors counterbalance the production: filling in the intracellular space that too much of histamine leaks, they turn off the tap, so to say. In other words, H2 and H3 receptors make sure that the production is not excessive. This is when they are healthy and active, when their population on the cells is adequate.
H2 receptor is especially important. Scientific sources state: “H2 receptor is a potent stimulant of cAMP production”. What is this cAMP? It is a pro-enzyme, on the activity of which functioning of about 80% of our genes depends. Wow! Like any organ in the body, our genes slow down in their work because of aging, wear and tear in the life process, severe stress of any kind - psychological, physical, environmental, etc. These genes are normal structurally, but they become "tired" and "exhausted". Correspondingly, the function they govern also slows down. We do not need to manipulate with the genes. We need to find the way to activate them by some chemical or action. cAMP, which supervises the activity of so many genes would be the best target. Histamine H2 receptor has direct access to cAMP, and no other substance in our body can activate this pro-enzyme the way histamine can. Thus, if we could stimulate cAMP with histamine, we could activate up to 80% of the genes! It makes H2 receptor truly unique. It makes histamine unique as well if its receptor can push lazy genes into activity.
Where are these H2 receptors situated? Everywhere: in the brain, in the gut, muscles, vessels, etc. All immune cells have this receptor, and the more, the better it is for the person. Thus, the leakage of histamine can be explained simply by inactivity or scarcity of H2 receptors. Why are they inactive? Simply because we are imperfect by nature but notice our flaws when they are outside, while those inside do not strike our eye. We get to know about them through symptoms, signs, and manifestations. We get many of our defects/deficiencies from our parents with the genes. Look back at your parents or siblings: the majority of migraine sufferers have one and the same defect in their family even if the manifestation in may not be a headache. Since all organs and tissues depend on histamine production, any of them may manifest with its specific symptoms: lungs - cough; nose - sneezing or stuffiness; skin - itch, brain - headache, etc. The more elaborate the cell, the more histamine it produces. Neurons produce a lot of it.
Now, before drawing conclusions and blaming H2 receptor for its deficient work, let’s finish with other histamine receptors. H3 receptor is similar to H2 receptor in that is also moderates the production of histamine by the cell and is thus an opponent of H1 receptor. The main concentration of H3 receptors is on nerve cells. It works synergistically with H2 receptor but does not have an access to the genes H2 receptor has.
H4 receptor mostly concentrates in bone marrow and white blood cells and regulates neutrophil release from bone marrow. In other words, it is busy with blood cells creation, and we’ll not dwell on it since it does not participate in migraines and related diseases.
As a conclusion: histamine is a substance produced by all parts of the body and vital for the functioning of the immune system, the brain activity and even affecting the activity of 80% of our genes. If H2/3 receptors are scarce or underdeveloped, H1 receptors react disproportionally, and histamine is produced in larger than normal amounts we suffer from pains, headaches, allergies and asthma. Does it mean we need antihistamines to suppress the activity of NORMAL H1 receptors? Their signals are too strong only because the "turn-off" receptors, H2/3, are not efficient enough.
