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Biogenic amines are the amines found in the biological system with many vital functions and roles. First, let me describe what is an amine? Amines are the organic compounds containing an amino group as a functional group. They are basically considered as a derivative of ammonia in which one or more than one hydrogen atom is replaced by a substituent and therefore amines can be primary, secondary and tertiary depending on the number of substituents. Amines can be alkyl or aryl depending on the type of substituent attached. There are some of the most important biogenic amines in our system that are playing the vital role in various physiological and metabolic processes as described below.
Histamine is one of the most important biogenic amines that is involved in the local immune response to various allergens. It is synthesized from the histidine by the action of L-histidine decarboxylase. After synthesis, histamine can either be stored in the form of granules inside the mast cells and basophils or can be rapidly inactivated by histamine-N-methyltransferase. Histamine is primarily an immunologically active compound but it also acts as a neurotransmitter in the brain and central nervous system where it is secreted from the non-mast cells. It acts via the G-protein linked cell surface receptors (Histamine receptor H1 to H4).
Histamine-activated G-protein linked cell surface receptor activates the G protein that initiates the signaling cascade via phospholipase C and the phosphatidylinositol pathway controlling the expression of the transcription factor, NF-κB, responsible for the inflammation processes. Therefore, antihistamines act on the receptor and stop the expression of the transcription factor responsible for the inflammation.
During the inflammatory responses mediated by different allergens and pathogens, immune cells such as basophils, release histamine in a large amount that leads to the hypersensitivity reaction. The symptoms may include redness of the skin and etching. Besides the immunological action, histamine plays several other roles such as vasodilation, lowering of blood pressure, gastric acid release, sleep-wake regulation, schizophrenia, multiple sclerosis, etc.
Serotonin, which is also called as 5-hydroxytryptamine (5-HT), is a biogenic amine derived from L-tryptophan. It is a potent neurotransmitter best known for its contribution to the feelings of being happy and love. About 90 % of the serotonin is secreted in the enterochromaffin cells of the gastrointestinal tract where it regulates the intestinal movement. The rest of the serotonin is secreted by the serotonergic neurons of the central nervous system where it has many other functions including the regulation of mood, sleep, and appetite.
Serotonin secreted by the enterochromaffin cells into the gastrointestinal tract is finally absorbed by blood platelets. Platelets release the serotonin once they bind to a clot where serotonin serves as a vasoconstrictor thereby regulating homeostasis and blood clotting mechanism.
Serotonin is synthesized from L-tryptophan in a series of reactions catalyzed by enzymes. L-tryptophan is first converted into 5-Hydroxy-L-Tryptophan (5-HTP) catalyzed by tryptophan hydroxylase. In the next step, 5-HTP is converted into serotonin catalyzed by aromatic L-amino acid decarboxylase. Serotonin exerts its effects via the 5-HT receptors. These receptors are the G-protein linked cell surface receptors located in the neurons of central and peripheral nervous system. The activated 5-HT receptors initiate a series of downstream signaling cascade leading to the expression of various enzymes responsible for the synthesis of other neurotransmitters.
Dopamine is another type of amine belonging to the class of biogenic amines. The full name of dopamine is 3,4-dihydroxyphenethylamine. It is a primary aromatic amine that is derived from L-tyrosine. In neurons and cells of the adrenal gland, L-tyrosine is converted to the L-DOPA (L-dihydroxyphenylalanine) catalyzed by the L-tyrosine hydroxylase. L-DOPA is the direct precursor of the dopamine. Formation of the dopamine from L-DOPA is catalyzed by the DOPA decarboxylase. This is the rate-limiting step of the dopamine biosynthesis as well as other related products such as epinephrine and norepinephrine.
In the brain, dopamine acts as a neurotransmitter transmitting signal from one neuron to another. It is one of the three hormones (neuromodulatory hormones) that in coordination with one another controls depression, love, and happiness. Other functions of the dopamine outside of the central nervous system include chemical messenger and vasodilator. It inhibits the release of norepinephrine in blood vessels and promotes the excretion of sodium and urine output while it decreases the production of insulin and gastrointestinal mobility.
Dopamine acts via the dopamine receptor (which is 5 types D1 to D5). These dopamine receptors belong to the G-protein-linked cell-surface receptor superfamily in which cell surface receptor is activated when the ligand binds to the respective receptor. After synthesis, dopamine is transported from the cytosol to the synaptic vesicles via solute carriers. In the synaptic cleft, these vesicles release the dopamine into the synapse where it binds to the dopamine receptors and initiates the signaling cascade leading to the expression of neuromodulatory proteins.