Histamine - More than just a runny nose!
by Michael Charles Hatch email@example.com
If you have an allergy, chances are you've heard of histamine. It is a amine produced by your body that is used to maintain homeostasis. It is also a neurotransmitter and plays a role in your immune system by acting as a white cell director. Histamine imbalances in your body cause a variety of effects. Histamine shortages (Histapenia) causes effects ranging from heavy body hair growth and headaches to anaphylactic shock paranoia. Histamine abundance (Histadelia) in the body also causes a variety of effect ranging from the mundane (such as phobias, seasonal allergies and an increased metabolism) to the serious (like chronic depression).
Histamine was first discovered in 1910 by Sir Henry Hallett Dale as a contaminant of ergot generated by bacterial action. It was first synthesised before its significance was known, and due to its wide range of biological activity, has become one of the most important biologically produced amines in medicine and biology. The word histamine comes from histos, which means tissue. By 1937, the first "antihistamine" had been synthesised by Etienne Fourneau, which was the H1 receptor (c.f. here) antagonist, thymo-ethyl-diethylamine. However it was found to not have a strong enough activity, and was too toxic for clinical use in the treatment of Histadelia. In 1942, Bernard N. Halpem synthesised the first clincally used antihistamine - phenbenzamine.
Histamine in the Body
In the body, histamine is synthesised by the enzyme catalysed decarboxylation of the amino acid histidine. It is then either stored, used in activating a receptor, or is broken down. Histamine is stored in several places around the body, mainly in mast cells (which themselves are found in abundance around areas particularly prone to injury, such as blood vessels and extremities) and basophils (which are a type of white blood cell found in the blood stream). Histamine from these sources is used mainly as part of your body's immune system where the histamine release is stimulated by Immunoglobulin E, a type of mammalian antibody, and then has an effect depending upon the receptor it comes into contact with. There are four known receptors: H1 - H4 The receptor that the histamine reacts with is dependant upon where the histamine is released in the body.
mast cells, from http://en.wikipedia.org/wiki/Mast_cells
H1 - Histamine Receptors: One of the most important receptors for modulating your internal clock and a main target for many clinical drugs. When histamine reacts with these receptors in your brain, it alters your neurochemistry to make you more awake and alert. This is why antihistamines cause drowsiness, as they oppose the reaction of histamine with the H1 receptors. In other areas of yur body, stimulation of these receptors causes hives, broncho-constriction, motion sickness, separation of the cells lining of blood vessels and smooth muscle relaxation (and consequently vasodilation - the widening of blood vessels) . Excess activation of these receptors triggers the symptoms of hayfever and other seasonal allergies.
H2 - Histamine Receptors: Found on parietal cells, located in the stomach lining and are mainly responsible for regulating levels of gastric acid. Histamine action at these receptors on parietal cells stimulates the release gastric acid, excess of which can result in stomach flu. These receptors are also found on heart, uterus and vascular smooth muscle cells. Histamine reacting with the receptor at these places encourages smooth muscle relaxation. H2 recpetors can finally be found on Neutrophils (the most common type of white blood cell). Histamine can also inhibit antibody and cytokine production by reacting with these receptors.
H3 - Histamine Receptors: These are present throughout the nervous system, though most notably in the central nervous system. They regulate histamine in the body, by inhibiting the further synthesis of histamine. The more of these receptors are triggered by histamine, the less histamine is produced in the body.
H4 - Histamine Receptors: Discovered in 2001, these receptors regulate the levels of white blood cell release from bone marrow. They have also been show to direct mast cells. They are located in the thymus, small intestine, spleen, the colon, bone marrow and basophils.
image showing H1 receptors in the brain from www.fmbe.coe.tohoku.ac.jp/studies/ibms/kyana-en.html
Wikipedia - http://en.wikipedia.org/wiki/Histamine
Histamine: Biological and Medical Aspects, A Falus