When you think of the neurotransmitter serotonin, you think of mood, happiness, depression, and antidepressants. Paxil, Prozac, and Zoloft, to name a few. Some people would argue that the United States truly is a Prozac nation. We sure do love our antidepressants; the number of Americans that are on SSRI medications has dramatically increased over the years.[1]
Serotonin is a neurotransmitter that is derived from the amino acid tryptophan. Our gastrointestinal tract, muscles, blood cells, and central nervous system use serotonin. Approximately ninety percent of our total serotonin is produced within our gastrointestinal tract (by our enterochromaffin cells and microbiome), where it regulates intestinal muscular contractions. Our microbiome also produces serotonin in differing amounts. Some of the produced serotonin within our digestive tract enters our bloodstream, which is stored in red blood cells. The serotonin produced outside of our brain cannot cross the blood-brain barrier. However, serotonin precursors 5-HTP and L-tryptophan can cross the blood-brain barrier. Serotonin is believed to regulate mood, appetite, and wakefulness. Our cells have different receptors for serotonin (known as 5-HT receptors), and how serotonin interacts with our cells and what it does for us depends on the type of receptor.[2] [3] [4] [5]
How do we produce serotonin? The amino acid L-tryptophan that we have ingest is hydroxylated into 5- hydroxytryptophan by the enzyme tryptophan hydroxylase type two. 5- hydroxytryptophan is then decarboxylated by the enzyme l-aromatic acid decarboxylase into serotonin, and the amount is rate limited depending on how much sunlight or artificial blue light we are exposed to (both increase serotonin production, sunlight is optimal). Some of our serotonin is later converted into melatonin, and the rest is broken down and eliminated from our bodies. The liver metabolizes serotonin. Monoamine oxidase metabolizes serotonin into an aldehyde, further broken down by aldehyde dehydrogenase into 5-HIAA. Our kidneys express 5-HIAA into our urine, which is expelled from the body. For proper serotonin homeostasis, serotonin must be balanced within our blood plasma and the amount within our cells, neurons, and tissues. Finally, the mechanism of action of SSRIs is the inhibition of the reuptake of serotonin, decreasing the reabsorption of serotonin into the neuron that released it and prolonging its availability in the synaptic cleft to be used by our body.[6] [7] [8]
What does serotonin do for us?[9] [10] [11] [12] [13] [14]
Serotonin promotes wakefulness and is integral to our day/night circadian rhythm cycle. The greater the length and brighter the sunlight you are exposed to during the day, the more serotonin will be produced. When serotonin is elevated, melatonin decreases, helping us maintain alertness.
Serotonin towards the evening is acetylated and then methylated into melatonin by the pineal gland, a hormone that is also an essential part of our day/night circadian rhythm cycle and contributes to proper sleep. During reduced light exposure and in the absence of light (nighttime), the suprachiasmatic nucleus within the hypothalamus alerts the pituitary gland to convert serotonin into melatonin. The enzyme serotonin N-acetyltransferase within the pituitary gland acetylates serotonin into N-acetylserotonin, known as normelatonin. Normelatonin is methylated by the enzyme acetylserotonin O-methyltransferase into melatonin, also within the pineal gland.
Serotonin production regulates bone mass, remodeling, and growth.
Serotonin suppresses appetite and leads to satiety.
Proper serotonin homeostasis is essential for heart health. Serotonin is stored in our blood platelets. Serotonin helps to initiate proper blood clotting (platelet aggregating). Serotonin can both increase and decrease blood pressure. It can decrease blood pressure as a vasodilator by increasing nitric oxide synthesis and blood pressure through platelet aggregation.
Serotonin is needed for proper muscular contraction.
Serotonin increases the function of the migrating motor complex in the intestines as a muscular contractor. Serotonin triggers nausea and vomiting by activating the 5-HT3 receptors within the chemoreceptor trigger zone of the medulla oblongata.
Serotonin reduces body temperature through vasodilation.
Serotonin induces bronchoconstriction.
Serotonin induces uterine contractions.
Serotonin contributes to mood stabilization in combination with other neurotransmitters.
Serotonin helps to regulate our libido. In women, elevated serotonin may modulate inhibitory pathways and decrease sexual libido. SSRIs reduce libido as a side effect of the medications, especially for women.
Serotonin decreases the sensation of nerve pain. The activation of serotonin-1A receptors inhibits glutamate release from the sensory neurons reducing pain transmission.
Serotonin is essential for liver regeneration and stabilization of liver transplantation by improving or restoring blood flow to the liver. Adequate blood flow to the liver promotes tissue repair. However, excess serotonin harms your health if you have liver cancer by increasing blood circulation to your tumor.
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