Serotonin transporter-linked

Huang YY, Simpson N, Arcement J, Huang Y, Ogden RT, 78. et al. Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain. Am. J. Psychiatry 2006 163 48-51. 79. 

Masoliver F. Menoyo A, Perez V, et al. Serotonin transporter linked promoter (polymorphism) in the serotonin transporter gene may be associated with antidepressant-induced mania in bipolar disorder. Psychiatr Genet 2006 16 25-9. 

Yoshida, K., Ito, K. etal. (2002). Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26(2), 383-6. 

Ribeiro, P. and Webb, R.A. (1987) Characterization of a serotonin transporter and an adenylate cyclase-linked serotonin receptor in the cestode Hymenolepis diminuta. Life Sciences 40, 755-768. 

For years, scientists have known that cocaine interferes with the brain s dopamine system. Dopamine is a neurotransmitter—a chemical that passes nerve impulses from one nerve cell to another, and dopamine is associated with movement, emotional response, and the ability to experience pleasure. Research indicates that serotonin transporters are also inactivated with cocaine use. Serotonin is another neurotransmitter, and adequate levels are associated with well-being. Low levels of serotonin in the brain have been linked to depression. Inactivation of dopamine and serotonin transporters leads to receptor over-stimulation and the high. Continued use of cocaine can result in long-term changes in the brain chemistry as receptors decrease in number. These changes can be persistent and even irreversible, and may be responsible for the feeling of depression that lasts long after withdrawal. 

Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006) Serotonin transporter promoter gain-of-fimction genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 78 815-826... 

Falls SSRIs and serotonin and noradrenalin reuptake inhibitors (SNRIs) have long been linked with an increased risk of osteopenia/osteoporosis potentiating falls and fractures, especially in tiie elderly. A biological mechanism for these risks associated with SSRIs has been idenhfied. Studies have demonstrated a reduction in osteoblast proliferation and activity following treatment with SSRIs, the magnitude of such effects being linked to affinity to the serotonin transporter. In addition, recent research examining serotonin receptor expression in human osteoblasts and osteoclasts has found that SSRIs differentially inhibit bone cells via apoptosis [10 ]. 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Pyridoxal phosphate is a required coenzyme for many enzyme-catalyzed reactions. Most of these reactions are associated with the metabolism of amino acids, including the decarboxylation reactions involved in the synthesis of the neurotransmitters dopamine and serotonin. In addition, pyridoxal phosphate is required for a key step in the synthesis of porphyrins, including the heme group that is an essential player in the transport of molecular oxygen by hemoglobin. Finally, pyridoxal phosphate-dependent reactions link amino acid metabolism to the citric acid cycle (chapter 16). 

With the exception of acetylcholine, all the neurotransmitters shown in Figure 7-41 are removed from the synaptic cleft by transport into the axon terminals that released them. Thus these transmitters are recycled Intact, as depicted in Figure 7-42 (step 5]). Transporters for GABA, norepinephrine, dopamine, and serotonin were the first to be cloned and studied. These four transport proteins are all Na -linked symporters. They are 60-70 percent Identical In their amino acid sequences, and each is thought to contain 12 transmembrane a helices. As with other Na symporters, the movement of Na into the cell down Its electrochemical gradient provides the energy for uptake of the neurotransmlt-ter. To maintain electroneutrality, CM often Is transported via an ion channel along with the Na and neurotransmitter. 

Yes. Recent research has linked low levels of serotonin (and a related protein that transports serotonin around the brain) to depression in humans and laboratory mice. It can also lead to symptoms such as apathy, fear, feelings of worthlessness, insomnia and fatigue. 

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