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Topic: HSERT

In the News (Fri 17 Feb 12)

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	SLC6A4 - solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
		In this study, the hypothesis was partially investigated by determining the potencies of haloperidol and reduced haloperidol and the corresponding pyridinium and tetrahydropyridine metabolites, compared with MPP+ and MPTP, as inhibitors of the noradrenaline transporter (NAT), dopamine transporter (DAT) and 5-HT transporter (SERT).
		Polymorphisms in the regulatory region of the serotonin transporter (5-HTT), in intron 7 of the tryptophan hydroxylase (TPH) gene and in the MAOA gene were previously reported to be associated with mood and anxiety disorders, impulsivity and aggression.
		Using quantitative autoradiography, we found that 5HT3 receptors are upregulated in frontal cortex (+46%), parietal cortex (+42%), and in stratum oriens of the CA3 region of the hippocampus (+18%) of 5HTT knockout mice.
	www.ihop-net.org /UniPub/iHOP/gg/92210.html (6933 words)

	SerT -
		In marked contrast to the human SERT (hSERT), 5HT-mediated transport by dSERT was not absolutely dependent on extracellular Cl-, while the sodium-dependent uptake of 5HT was facilitated by increased extracellular Cl- concentrations.
		Comparison of the affinities of various compounds for the inhibition of 5HT transport by both dSERT and hSERT revealed that antidepressants were 3- to 300-fold less potent on dSERT than on hSERT, while mazindol displayed approximately 30-fold greater potency for dSERT.
		Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT).
	www.ihop-net.org /UniPub/iHOP/gg/63450.html (991 words)

	Serotonin transporter - Wikipedia, the free encyclopedia
		In humans, the serotonin transporter is encoded by the human serotonin transporter gene (hSERT).
		Researchers have found an uncommon mutation in hSERT, in some unrelated families with OCD, that leads to faulty transporter function and regulation.
		A second variant in the same gene of some patients with this mutation suggests a genetic "double hit," resulting in greater biochemical effects and more severe symptoms.
	en.wikipedia.org /wiki/Human_serotonin_transporter_gene (308 words)

	Mutant gene linked to obsessive compulsive disorder
		About half of patients with OCD are treated with SSRIs, but those with the hSERT gene defect do not seem to respond to them, according to the study.
		By examining the serotonin transporter gene's mutation and flawed regulation in individuals with OCD, the new research provides insights on transporter function and on the consequences of the variant, which may lead to tests to identify and treat mental illness.
		The mutant molecule was not regulated normally and did not respond to cell signals that activate the common form of the transporter.
	www.eurekalert.org /pub_releases/2003-10/niom-mgl102103.php (833 words)

	Obsessive Compulsive Gene hSERT - Mental Health Disorders on MedicineNet.com
		Researchers have found a mutation in the human serotonin transporter gene, hSERT, in unrelated families with OCD.
		Although rare, with the I425V mutation found in two unrelated families, the researchers propose it is likely to exist in other families with OCD and related disorders.
		In addition to the I425V mutation, the two original subjects and their two siblings had a particular form of another hSERT variant, two long alleles of the 5-HTTLPR polymorphism.
	www.medicinenet.com /script/main/art.asp?articlekey=24920 (901 words)

	Yale Daily News - Genetics may help explain OCD
		Serotonin is a neurotransmitter in the human body, which is released from one nerve cell and binds to receptors on the surface of the next cell to transmit a signal.
		The first mutation is in hSERT, and the second is in the promoter region of the gene, which determines how much of a protein is produced.
		If you think about all the time nature had to perfect the transporter, you wouldn't think a rare mutation would make it work better than it was evolved to work.
	www.yaledailynews.com /article.asp?AID=23926 (1171 words)

	Gene Mutation Linked to Obsessive Compulsive Disorder
		INKED TO Analysis of DNA samples from patients with obsessive compulsive disorder (OCD) and related illnesses suggests that these neuropsychiatric disorders affecting mood and behavior are associated with an uncommon gene mutation that leads to faulty transporter function and regulation, according to a report in the October 23, 2003, Molecular Psychiatry.
		The researchers found a mutation in the human serotonin transporter gene, hSERT, in unrelated families with obsessive compulsive disorder.
		Although rare, with the I425V mutation found in two unrelated families, the researchers proposed it is likely to exist in other families with obsessive compulsive disorder and related disorders.
	www.neuropsychiatryreviews.com /feb04/npr_feb04_genes.html (567 words)

	Phosphorylation and Sequestration of Serotonin Transporters Differentially Modulated by Psychostimulants -- Ramamoorthy ...
		hSERT activity (38) was assessed as a function of increasing concentrations of 5-HT in the presence of 200 nM
		The EC50 for the 5-HT block of hSERT phosphorylation was 68 ± 21 nM.
		These substitutions were also monitored for their impact on hSERT activity (bottom panel) (38).
	www.sciencemag.org /cgi/content/full/285/5428/763?ijkey=NxRbij5U3zMng (3509 words)

	Serotonin Transporters: Implications for Antidepressant Drug Development
		Using species-scanning mutagenesis, F586 in hSERT was mutated to the corresponding valine in rSERT.
		The F586V hSERT mutant demonstrated a phenotype similar to the rSERT with regard to TCA potency.
		The hSERT I425V mutation results in increased 5-HT transport in human cervical epitheloid carcinoma and COS-7 cells transfected with the I425V hSERT cDNA.
	www.aapsj.org /view.asp?art=aapsj070242 (8406 words)

	Early Fluorescence Signals Detect Transitions at Mammalian Serotonin Transporters -- Li and Lester 83 (1): 206 -- ...
		The mammalian serotonin transporters rSERT or hSERT were expressed in oocytes and labeled with sulforhodamine-MTS.
		Note that the fluorescence change for the depolarizing step for rSERT consists of one phase occupying several hundred milliseconds, but for hSERT there are two distinct phases, including one phase occupying only tens of milliseconds.
		FIGURE 5 Fluorescence of sulforhodamine-labeled hSERT during voltage-jump relaxations in the absence (A) and presence (B) of 20 µM 5-HT.
	www.biophysj.org /cgi/content/full/83/1/206 (4778 words)

	MDMA Pharmacology -- Neurotransmitter.net
		Moreover, hSERT phosphorylation induced by beta-phorbol 12-myristate 13-acetate is abolished selectively by the PKC inhibitors staurosporine and bisindolylmaleimide I, whereas hSERT phosphorylation induced by phosphatase inhibitors is insensitive to these agents at comparable concentrations.
		Substrates of the hSERT [e.g., p-chloroamphetamine (PCA)], increased the basal efflux of [(3)H]5-HT in a concentration-dependent manner.
		The addition of the Na(+),K(+)-ATPase inhibitor ouabain (100 microM) to the superfusion buffer enhanced basal efflux of [(3)H]5-HT-loaded hSERT cells by approximately 2-fold; the effect of PCA (10 microM) was strongly augmented by ouabain, whereas the effect of imipramine was not.
	www.neurotransmitter.net /mdma.html (16459 words)

	Recognition of Psychostimulants, Antidepressants, and Other Inhibitors of Synaptic Neurotransmitter Uptake by the ...
		Thus, hDAT D68, hSERT D87, and hNET D64 are found at Position 34 in TM 1.
		The hSERT tyrosine residue is conserved in only 1 of the 4 GABA transporters, with a glutamate side chain occupying the position in GAT-2, -3 and -4.
		This hSERT phenylalanine residue is replaced by a valine side chain in other SERT species, and methionine in the DAT and NET.
	www.aapsj.org /view.asp?art=aapsj070374 (8303 words)

	Acta Pharmacologica Sinica
		These results might be used to explain the long-lasting anti-anxiety effect of fluoxetine in clinical practice, because it increases the concentration of 5-HT in the synaptic cleft by its enduring suppression of the function of 5-HT transporters.
		By using human serotonin transporters (hSERT) heterologously expressed in Xenopus oocytes, and the 2-electrode voltage clamp technique, we studied the dynamic changes of hSERT in the process of transporting 5-HT under the influence of fluoxetine.
		Stage V and VI defolliculated oocytes were injected with 52 nL (1 ng/nL) hSERT cRNA and then incubated at 19 °C in Ringer’s solution (pH 7.6) supplemented with 1% penicillin-streptomycin stock and 5% horse serum.
	www.chinaphar.com /1671-4083/27/289.htm (1999 words)

	RARE FORM OF OBSESSIVE COMPULSIVE DISORDER ASSOCIATED WITH GENE MUTATION
		It is released from one nerve cell into a synapse, or space, between nerves, then interacts with receptors on the surface of another cell to transmit the signal.
		When serotonin is released, the human serotonin transporter, hSERT, is responsible for removing serotonin from the synapse by transporting it back into the cell.
		Rudnick's group measured the activity of the mutant protein and found that the mutant protein was better than the normal protein at transporting serotonin.
	www.newmaterials.com /news/3378.asp (418 words)

	Phosphorylation and Regulation of Antidepressant-sensitive Serotonin Transporters -- Ramamoorthy et al. 273 (4): 2458 ...
		In the absence of phosphatase inhibitors or PKC activators (Fig.
		-PMA on the phosphorylation of hSERT and 5-HT uptake.
		-PMA, cholera toxin, and okadaic acid-induced phosphorylation of hSERT
	www.jbc.org /cgi/content/full/273/4/2458 (5483 words)

	Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein ...
		Variants were transfected in parallel with hSERT into HeLa cells, and cell surface transporters were identified by immunoblotting of biotinylated samples, captured as described in Materials and Methods.(C) Quantitative estimations of relative surface density of hSERT, Pro339Leu, and Ile425Val based on densitometry of biotinylation immunoblots.
		HeLa cells transfected with hSERT- or hSERT-coding variants were examined for 5-HT transport activities as described in Materials and Methods after pretreatments of cells with either 100 µM 8BrcGMP ± H8 or vehicle for 1 h.
		Data were analyzed by a one-way ANOVA with post hoc Bonferonni tests comparing variant to hSERT anisomycin responses, with P < 0.05 taken as significant.
	www.pnas.org /cgi/content/full/102/32/11545 (4310 words)

	Gene found for obsessive disorder - Genetics - MSNBC.com (Site not responding. Last check: 2007-10-23)
		A specific mutation in the hSERT gene was seen in two patients with OCD and their families, but not in other patients.
		They interviewed relatives of the patients and found 6 of the 7 people with the mutation had an obsessive-compulsive disorder, and some also had anorexia, Asperger’s syndrome, which is a form of autism, social phobia or were abusers of alcohol.
		A second mutation was found in hSERT in two patients, giving them a “double dose.” The patients and their siblings had especially difficult to treat versions of OCD, the researchers said.
	www.msnbc.msn.com /id/3341620 (456 words)

	Thioether Metabolites of 3,4-Methylenedioxyamphetamine and 3,4-Methylenedioxymethamphetamine Inhibit Human Serotonin ...
		ROS generation was determined in hSERT- (A) and hDAT (B)-transfected cells using increasing concentrations (10, 50, 100, 200, and 400 µM) of the compounds and by measuring increases in DCF fluorescence 4 h after treatment.
		ROS generation was determined in hSERT- (A) and hDAT (B)-transfected cells after a 4-h incubation with the compounds by measuring changes in DCF fluorescence.
		DA uptake by the hSERT is not known, Saldana and Barker (2004
	jpet.aspetjournals.org /cgi/content/full/311/1/298 (4367 words)

	Distinct Recognition of Substrates by the Human and Drosophila Serotonin Transporters -- Rodríguez et al. 306 ...
		A, diagram of wild-type hSERT, dSERT, and cross-species chimeras.
		H]mazindol (20 nM) was used for hSERT (A) and dSERT (B), respectively.
		H]5-HT (50 nM) for 5 min (hSERT) or 30 min (dSERT and cross-species chimeras), and exchange was induced by increasing the concentration of unlabeled substrate as described under Materials and Methods.
	jpet.aspetjournals.org /cgi/content/full/306/1/338 (4824 words)

	Serotonin Transporter Research -- Neurotransmitter.net
		The decrease in KM was accompanied by a decrease in the KD for binding of the cocaine analog 2beta-carbomethoxy-3beta-(4-[125I]iodophenyl)tropane.
		In both HeLa and COS-7 cells, the nitric oxide donor S-nitroso-N-acetylpenicillamine increased the activity of wild-type hSERT to that of the variant but did not change the activity of the I425V variant.
		The compounds were evaluated for their in vitro receptor binding properties toward human dopamine (hDAT) and serotonin (hSERT) transporters using [(3)H]WIN35,428 and [(3)H]citalopram as specific radioligands, respectively.
	www.neurotransmitter.net /reuptake.html (16362 words)

	Amino Acid Residues that Control pH Modulation of Transport-Associated Current in Mammalian Serotonin Transporters -- ...
		The hSERT cDNA was isolated by Dr. Beth J.
		Putative membrane topology is indicated by the blue (intracellular), white (transmembrane, N terminal near the intracellular face), pink (extracellular), and gray (transmembrane, N terminal near the extracellular face) regions.
		The oscillations in the final epoch of row 3 are an artifact of the algorithm that suppressed 60 Hz interference earlier in the traces.
	www.jneurosci.org /cgi/content/full/18/19/7739 (5583 words)

	Serotonin Transporter Function and Pharmacology Are Sensitive to Expression Level. EVIDENCE FOR AN ENDOGENOUS ...
		The relative densities of the mature surface hSERT
		The data are from oocytes injected with increasing amounts of SERT cRNA (0.41-41.4 ng/oocyte) and cultured for 2 days at 24 °C. representative Western blot showing hSERT protein in biotinylated (streptavidin bead-bound, +) and nonbiotinylated (unbound to streptavidin beads,
		The oocytes were injected with hSERT cRNA and cultured for 2 days at 24 °C. was measured during 2-min assays in the presence of 0.1 µ
	www.jbc.org /cgi/content/full/277/17/14475 (5109 words)

	Flux Coupling in the Human Serotonin Transporter -- Adams and DeFelice 83 (6): 3268 -- Biophysical Journal
		increases, the ability of hSERT to maintain a 5HT gradient decreases.
		FIGURE 7 Predictions of the 5HT gradient and unidirectional flux ratio produced by hSERT functioning as a single-file pore, permeable to 5HT and sodium, with n = 3 sites.
		It is possible that hSERT switches between strict
	www.biophysj.org /cgi/content/full/83/6/3268 (6487 words)

	X’s Prismatic Ponderings… » Blog Archive » Entrez PubMed
		The interaction of the S- and R-enantiomers (escitalopram and R-citalopram) of citalopram, with high- and low-affinity binding sites in COS-1 cell membranes expressing human SERT (hSERT) were investigated.
		Escitalopram affinity for hSERT and its 5-HT uptake inhibitory potency was in the nanomolar range and approximately 40-fold more potent than R-citalopram.
		This entry was posted on Friday, April 1st, 2005 at 5:42 pm and is filed under Neuropsychology.
	cxo.centosprime.com /wp?p=1968 (287 words)

	Cocaine and Antidepressant-Sensitive Biogenic Amine Transporters Exist in Regulated Complexes with Protein Phosphatase ...
		Phosphatase activity was measured in SERT (#48) immune complexes (n = 3), as described in Materials and Methods, and compared with activity found with nonimmune sera (*p < 0.05, Student's t test).
		Total cell extracts from 293 hSERT cells (250 µg) were immunoprecipitated overnight with SERT immune sera (#48) or preimmune sera (PI), and the resulting blot was probed with PP2Ac monoclonal antibody as described in Materials and Methods.
		Levels of PP2Ac in parental HEK-293 cell immunoprecipitates were equivalent to that seen with preimmune serum.
	www.jneurosci.org /cgi/content/full/20/20/7571 (6135 words)

	OCD Patients Stalked By Mutant Gene -- Rosack 38 (22): 26 -- Psychiatric News
		The report may be the first in which two mutations within the
		The hSERT gene codes for the human serotonin transporter—the
		The mutation appears to be associated with an increased
	pn.psychiatryonline.org /cgi/content/full/38/22/26?etoc (536 words)

	Ion channel Literature - Amino acid residues that control pH modulation of transport-associated current in mammalian ... (Site not responding. Last check: 2007-10-23)
		The rat and human serotonin transporters (rSERT and hSERT, respectively) were expressed in Xenopus oocytes and studied using site-directed mutagenesis, electrophysiological recordings, and [3H]5-HT uptake measurements.
		Chimeras and point mutations showed that, of the 52 nonidentical residues, a single residue at position 490 (threonine in rSERT and lysine in hSERT) governs this difference.
		Furthermore, potentiation required the glutamate residue at position 493.
	www.ionchannels.org /showabstract.php?pmid=9742144 (386 words)

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