Saturday, September 25, 2010

(In)famous histamine

Histamine, called by the chemists 2-(imidazol-4-yl)ethylamine, is located in many tissues of the body and even if its physiological function is too complex to be currently, completely understood, sure is that histamine plays a predominant role in the allergic inflammatory response of the body and in the regulation of the secretion of gastric acid.
Therefore, a huge effort has been done to the development of drugs (medicaments) that antagonize (stop) its effects and therefore reduce the allergic reaction of the body and/or help to the regulation of the gastric acid.
For a compound to have effect in the body, it has to interact in one way or another with the metabolic pathways. Usually this interaction happens between the compound, usually a small molecule (in this case histamine) and a big molecule, a protein (or an enzime, which are just a specialized kind of proteins).
The target protein is called receptor, and associated to the name of the small moleculle which is able to interact with it, therefore the proteins in the metabolic pathways which interact with the histamine moleculle are called histamine receptors.
In general, the receptors, these proteins, are inside of the body, in the cells (or in the body fluids) but no necesarilly everywhereor in the same amount. For example, some receptors are present in the muscle cells but not in the nervous system and so on.
The histamine receptors can be found amongst other in the smooth muscle of the bronchi, gut and uterus, in the central nervous system and in the stomach.
These receptors are proteins, and proteins are very peculiar moleculles. They can be different in respect of the little, small pieces they are made but and the end, they perform the same function due to their final shape (to kept it easy). Also or maybe for this reason they are proteins which are a bit different from each other but that perform more or less the same function, for example histamine receptors, there is not only one unique histamine receptor in the universe. Different living being have different proteins as the proteins are given by the genetic code which is different in every living being, but even inside of the same body, there are histamine receptors which even if they interact with histamine, they are a bit different from each other. They are called receptor types (or even sub-types).
For the family of the histamine receptors only four receptor types are known, called H1, H2, H3 and H4.
This nomenclature is kind of common, some capital letters (H for histamine) and a number which usually denotes the other of discovery of the receptor.
Different receptor types of receptor are present (expressed) in different cells (tisues, parts of the body) and asociated to different metabolic effects (allergic response or secretion of gastric acid).
Histamine will, obviously interact (bind, anchor) with all these receptor types (and subtypes) and therefore histamine is an in-expecific moleculle (sometimes called substrate).
As every receptor type is expressed in different cells and regulates different metabolic effects, for the development of new drugs it is of primordial importance to create moleculles which are able to bind in a specific and selective way only one of the receptor types (or subtypes) so that for example, the allergic reaction can be blocked without disturbing the secretion of gastric acid.
Known Facts about the histamine receptor types are:
  • H1: to be found in the smooth muscle of the bronchi, wherein it regulates the contraction of the bronchi which leads to restriction of air flow in the lungs (if you have asthma, you know how it feels). Also the permeability of the capillary walls is regulated so that plasma constituents could flow into the extracellular spaces and produce an edema (basically the lungs are flodded with liquid and respiration becomes difficult). This receptor is also in the Central Nervous System wherein it is associated with drowsiness or somnolence. Drugs able to interact with this receptor are useful in the treatment of allergy and inflammation.
  • H2: plays a minor role in allergic inflammatory processes but in the stomach, parietal cells (the cells in the wall of the stomach) stimulation increases production and secretion of acid. Drugs able to interact with this receptor are useful in the treatment of ulcers.
  • H3: occurs in the brain, and it activation leads to a decrease in neurotransmiter release which promotes arousal, attention and improves learning (at least in animals). Allergic rhinitis is one condition in which drugs able to interact with this receptor may be useful.
  • H4: the more obscure, appears to be limited to cells of the hematopoietic (or hematogenesis, formation of blood) system and its stimulation results in a chemotactic response (movement or orientation of an organism or cell along a chemical concentration gradient either toward or away from the chemical stimulus, basically cell migration). The presence of this receptor on these cells suggests that this receptor plays a role in the inflammatory response.

Enough for today :)


Jokin said...

Are we working on new antihistaminic drug? :·)

Ariano said...

Sorry for the delay, but not really, just got something to read about it and thought about blogging something about drugs :D :D
The idea was to blogg more about other drugs but run out of time...