Serotonin

Serotonin is a neurotransmitter and a hormone that plays an important role in numerous life processes, including mood, sleep, appetite, temperature regulation, pain perception, sexual behavior, and the secretion of other hormones. It is derived from the essential amino acid tryptophan. Although most of the body's serotonin is found in the gastrointestinal system and in blood platelets, its most well-known effects are in the brain. Several types of psychoactive medications are known to alter the way serotonin is handled by the body; these medications can improve symptoms in people suffering from anxiety, depression, and bipolar disorder.

Contents 1 Other Names 2 Description 3 Roles of Serotonin in the Body 3.1 Roles in the brain 3.2 Roles in the intestine 3.3 Roles in the blood 4 Diseases related to Serotonin 5 History 6 References 7 External Link

Other Names

• 5-hydroxytryptamine
• 5-HT
• Enteramine
• Antemoqua
• Antemovis
• Hippophain
• 3-(beta-aminoethyl)-5-hydroxyindole

Description

Serotonin is a small molecule that is synthesized in specialized cells of the central nervous system and intestines; it is also found in blood platelets in the body and is present in many fruits and vegetables. It is derived from the amino acid tryptophan, and acts as both a neurotransmitter and a hormone.

Roles of Serotonin in the Body

Serotonin acts as both a neurotransmitter and a hormone. In both roles, it is released by one cell and carries a signal to another: as a neurotransmitter, the cell that receives the signal is a neuron; as a hormone, the signal-transmitting and signal-receiving cells are not adjacent and not neurons. The tremendous scope and variety of serotonin's effects come from the diversity of serotonin receptors, which exist on the serotonin-responsive cells and interact with serotonin.There are at least 15 different serotonin receptors.

Roles in the brain

Serotonin receptors in the brain are responsible for the the widely-known effects of this molecule on mood and the sometimes profound effects caused by serotonin-based psychiatric medications. Of these medications, the most important type are the selective serotonin reuptake inhibitors (SSRIs), of which fluoxetine (Prozac) is the prime example. Interference or augmentation of serotonin in the brain is the basis of drugs for schizophrenia, obsessive-compulsive disorder, anxiety, and others.

Roles in the intestine

Serotonin is an important signaling molecule in the gastrointestinal (GI) system, where it functions to initiate gut motility, allow the stomach to expand, and transmit information to the CNS.^[1] Drugs that either block (antagonists) or stimulate (agonists) specific serotonin receptor subtypes in the gut have been approved for certain GI disorders; examples include tegaserod (Zelnorm), granisetron (Kytril), ondansetron (Zofran), and alosetron (Lotronex). Tegaserod is a partial agonist of the 5-HT(4) receptor and is approved for treatment of irritable bowel syndrome (IBS) and chronic constipation. Granisetron and ondansetron are used in treating nausea associated with cancer chemotherapy. Alosetron is used in the treatment of IBS with diarrhea. Serotonin also plays a role in the stomach, where it acts on 5-HT(1) receptors to allow the stomach to expand.

Roles in the blood

Serotonin is stored in granules of platelets, which are specialized cell fragments that participate in blood clot formation. The widespread use of SSRIs for depression provided a sizable pool of patients who could be followed in epidemiologic studies, and it was soon noted that patients being treated with SSRIs who had a history of yocardial infarction (MI) had a remarkably lower risk of recurrent MI.^[2] The use of SSRIs in treatment of patients with acute coronary syndrome is associaetd with reduced rates of recurrent ischemia or heart failure , but carries an increased risk of bleeding.^[3] The importance of serotonin in the blood is also illustrated by patients with serotonin-deficient platelets, who are unable to form stable blood clots and are at increased risk for life-threatening bleeding episodes.

Diseases related to Serotonin

Excess serotonin may result in serotonin syndrome, which can be life-threatening. A typical case of serotonin syndrome is one where patients abruptly increase the dose of medications that increase serotonin levels, or add a serotonin-influencing drug to an existing routine.^[4] Clinical features of serotonin syndrome are divided into psychic, autonomic, and neuromuscular symptoms. Psychic symptoms of excess serotonin include confusion, hyperactivity, and restlessness; autonomic symptoms may include fever and sweating; neuromuscular symptoms may include increased reflexes (hyperreflexia), tremor, and shivering.^[5] The treatment always includes discontinuation of medications that increase serotonin levels. Serotonin antagonists such as cyproheptadine^[6] and mirtazapine^[7] have also been studied for treatment of serotonin syndrome.

History

Serotonin was isolated and characterized in 1948 by Maurice M. Rapport and colleagues in 1948.^[8] The initial purification used beef serum as the starting material and was based on serotonin's abundance in blood platelets and its ability to constrict blood vessels. Serotonin was named based on its initial purification from serum (sero-) and its ability to increase the tone of blood vessels (-tonin). The initial studies and naming did not anticipate the molecule's profound effects in the brain, and serotonin is sometimes referred to as a molecule of happiness.

The discovery of how 5-HT is synthesized and degraded led to the hypothesis that the symptoms of patients with carcinoid syndrome result from abnormally high production of serotonin. The effects of 5-HT suggested some of the physiologic and pharmacologic actions of 5-HT.^[9] For example, patients with carcinoid syndrome often display psychotic behaviors similar to those produced by lysergic acid diethylamide (LSD). Several naturally occurring hallucinogens (such as psilocybin) were identified from animal and plant sources, suggesting that these substances (or related molecules) might be formed in the body and account for the abnormal behavior of carcinoid patients. In the mid-1950s, 5-HT was proposed as a neurotransmitter in mammals.^[10]

References

1. ↑ Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007 Jan;132(1):397-414. Abstract
2. ↑ Maurer-Spurej E. Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection. Cell Mol Life Sci. 2005 Jan;62(2):159-70. Abstract
3. ↑ Ziegelstein RC, Meuchel J, Kim TJ, et al. Selective serotonin reuptake inhibitor use by patients with acute coronary syndromes. Am J Med. 2007 Jun;120(6):525-30. Abstract
4. ↑ Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review.CMAJ. 2003 May 27;168(11):1439-42. Citation | Full Text | PDF
5. ↑ Bijl D. The serotonin syndrome. Neth J Med. 2004 Oct;62(9):309-13. Abstract | PDF
6. ↑ Chan BS, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG. Serotonin syndrome resulting from drug interactions. Med J Aust. 1998 Nov 16;169(10):523-5. Abstract
7. ↑ Hoes MJ, Zeijpveld JH. Mirtazapine as treatment for serotonin syndrome. Pharmacopsychiatry. 1996 Mar;29(2):81. Citation
8. ↑ Rapport MM, Green AA, Page IH. Serum vasoconstrictor, serotonin; isolation and characterization. J Biol Chem. 1948 Dec;176(3):1243-51. Citation PDF
9. ↑ Sirek A, Sirek OV. Serotonin: a review. Can Med Assoc J. 1970 Apr 25;102(8):846-9. Abstract | PDF
10. ↑ Sjoerdsma A, Palfreyman MG. History of serotonin and serotinin disorders. Ann N Y Acad Sci. 1990;600:1-7; Citation

External Link

GoPubMed: What, Who, Where and When about Serotonin