The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membrane of synaptic vesicles of presynaptic neurons. It acts to transport monoamine neurotransmitters - such as dopamine, serotonin, norepinephrine, epinephrine, and histamine - into the vesicles, which release the neurotransmitters into synapses as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import. Pharmaceutical drugs that target VMATs have possible applications for many conditions, leading to a plethora of biological research. These applications include hypertension, drug addiction, psychiatric disorders, Parkinsons disease, and other neurological disorders. Many drugs that target VMAT act as inhibitors and alter the kinetics of the protein. Much research regarding the effects of altered VMATs on biological systems is still ongoing. The two VMAT isoforms are: VMAT1 VMAT2 Monoamines transported by VMATs are mainly ...
Wilson, J.M.; Carroll, M.E.; Kish, S.J., 1995: The vesicular monoamine transporter, in contrast to the dopamine transporter, is not regulated following chronic cocaine self-administration
In this study we investigated the regulation of the activity of the vesicular monoamine transporters VMAT1 and VMAT2 by heterotrimeric G-proteins. In the human neuroendocrine cell line BON both transporters are expressed. They colocalize in these cells with the a-subunit of the heterotrimeric G-protein Go2 predominantely on Large Dense Core Vesicles (LDCVs). The activity of both VMAT1 and VMAT2 is regulated by Gao2. G-protein activation results in a down-regulation of vesicular monoamine uptake. VMAT2 appears to be more sensitive towards the observed G-protein regulation than VMAT1. Serotonergic raphe neurons in primary culture express VMAT2 as the neuronal form of the transporter. In these neurons VMAT2 predominantely localizes to Small Synaptic Vesicles (SSVs). Here, VMAT2 colocalizes with Gao2 on SSVs. In these neurons Gao2-dependent down-regulation of VMAT2 activity was observed, too. Immunoelectron microscopic analysis confirmed a localization of VMAT2 and Gao2 on SSVs from serotonergic ...
The vesicular monoamine transporter 1 (VMAT1) is essential for storage of monoamines, such as epinephrine and serotonin, in secretory vesicles of neuroendocrine cells. Recently the VMAT1 protein was detected in human and mouse brain, and mutations of the VMAT1 gene at single DNA nucleotides (single nucleotide polymorphisms or SNPs) were associated with schizophrenia. In this study, Chinese hamster ovarian cells were stably transfected with either human VMAT1 DNA (GenBank: #NM_003053.1 or DNA with the Thr4Pro SNP, which results in a threonine to proline change in amino acid number 4 of the VMAT1 protein. Western blot analysis revealed that cells with the SNP produced immunoreactive human VMAT1 proteins of altered molecular size, suggesting that SNP Thr4Pro modifies either folding or processing of the VMAT1 protein. This finding is the first evidence for biochemical consequences of a mutation in the human VMAT1 gene.
Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a ...
In general, DA, after its synthesis, is taken up and stored in specialized subcellular organelles, the storage granules, to ensure its regulated release via exocytosis. Most information about the granular transport mechanism(s) and storage mechanism(s) of DA (and monoamines in general) has been obtained by using chromaffin granules isolated from adrenal medullary cells or PC12 cells as experimental substrate (Roda et al., 1980). Thus, it is presently known that the DAergic granular transport system consists of at least two components: (1) a so-called vesicular monoamine transporter (VMAT), structurally distinct from the plasma membrane DA transporter, and (2) a vacuolar-type ATP-driven H+ pump, which provides the electrochemical gradient on which the transporter depends for its function (Johnson, 1988; Schuldiner, 1994). Drugs such as reserpine and tetrabenazine deplete intracellular DA stores by selectively interfering with transmitter uptake via the VMAT. In the present set of experiments, we ...
Aromatic l-amino acid decarboxylase (AADC) converts l-5-hydroxytryptophan to 5HT; it is widely distributed and has broad substrate specificity. The synthesized product, 5HT, is accumulated in secretory granules by a vesicular monoamine transporter (VMAT2); vesicular 5HT is released by exocytosis from serotonergic neurons. In the nervous system, the action of released 5HT is terminated via neuronal uptake by a specific 5HT transporter (SERT), localized in the membrane of serotonergic axon terminals and in the membrane of platelets. This uptake system is the means by which platelets acquire 5HT, since they lack the enzymes required for 5HT synthesis. The amine transporters are distinct from VMAT2, which concentrates amines in intracellular storage vesicles and is a nonspecific amine carrier, whereas the 5HT transporter is specific. ...
The effects of lobeline on the acute and long-term effects of a high-dose METH regimen were examined. Preadministration of lobeline did not alter METH-induced dopamine release in vivo but attenuated the hyperthermia produced by METH, the rapid decrease in VMAT immunoreactivity, and the long-term depletions in striatal dopamine and 5HT content. Administration of lobeline at time points after METH when hyperthermia had dissipated also protected against METH-induced decreases in VMAT immunoreactivity and the long-term depletions of dopamine and 5HT content.. Systemic administration of lobeline did not affect basal or METH-induced increases in extracellular dopamine (Fig. 1). These results appear to be in contrast to previous findings indicating that intrastriatal infusion of lobeline increased dopamine release (Lecca et al., 2000), whereas systemic lobeline administration attenuated the locomotor hyperactivity after METH and decreased METH self-administration (Harrod et al., 2001; Miller et al., ...
Antisera. An affinity-purified rabbit polyclonal antiserum directed against a synthetic peptide [(C)SYPIGDDEESESD] at the C terminus of VMAT2 was raised in rabbits as described previously (Peter et al., 1995). The specificity of this antiserum has been demonstrated by Western blot analysis and immunocytochemistry (Nirenberg et al., 1995; Peter et al., 1995). A well characterized mouse monoclonal antiserum directed against TH was purchased from Incstar (Stillwater, MN).. Tissue preparation. The methods for tissue preparation and immunolabeling were based on those of Leranth and Pickel (1989). Four adult male Sprague-Dawley rats (250-400 gm; Taconic Farms, Germantown, NY) were anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and perfused through the ascending aorta with 40 ml of heparin (1000 U/ml heparin in 0.15 m NaCl) and 50 ml of 3.75% acrolein, followed by 200 ml of 2% paraformaldehyde in 0.1 m phosphate buffer (PB), pH 7.4. The brains were removed and postfixed for 30 min in 2% ...
The idea of targeting cancer therapeutics towards specific mutations or abnormalities in tumor cells which are not found in normal tissues has the potential advantages of high selectivity for the tumor and correspondingly low secondary toxicities. pathways of Ras such as growth factor receptors or PI3-Kinase and Raf/MAP kinases. We previously reported that aberrant activation of Ras signaling sensitizes cells to apoptosis when the activity of the PKCδ isozyme is usually suppressed and that PKCδ suppression is not harmful to cells with normal levels of p21Ras signaling. We demonstrate here that inhibition of PKCδ by a number of unbiased means including hereditary systems (shRNA) or little molecule inhibitors can effectively and selectively repress the development of individual neuroendocrine cell lines produced from bronchopulmonary foregut or hindgut tumors. PKCδ inhibition in these tumors efficiently induced apoptosis also. Contact with small-molecule Troxacitabine inhibitors Rabbit ...
The Conus genus includes around 500 species of marine mollusks using a peculiar production of venomous peptides referred to as conotoxins (CTX). S1) living generally in the tropical marine areas. About 700 species of Cone snails express hundreds of peptide toxins collectively known as conotoxins (CTX) aimed to self-defense, competition and predation of other marine species by means of stingCstructures that were reported to be fatal for human since from 300 years ago. CTX, however, do not exert only venomous activity but have a lot of pharmacological properties with specific bioactivity in the treatment of neurological disorders and the associated pain belief [1,2,3]. The presence of disulfide bonds is the important characteristic for natural function of CTX that enable to separate CTX into two primary types, the disulfide-rich peptides and no-disulfide-rich types; the foremost is generally composed of no more than 30 proteins and the next contains as much as 80 proteins. CTX are grouped into ...
The dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters, which are collectively referred to as monoamine transporters (MATs), play significant roles in regulating the neuronal response to these neurotransmitters
The aim of the present study was to analyze and to compare quantitative aspects of inward and outward transport of substrates by the human SERT to obtain more insight into the mechanisms of carrier-mediated release. As in our previous study on the rat (Sitte et al., 2000) and human SERT (Scholze et al., 2000), we used the natural substrate 5-HT, and MPP+, a commonly used substrate for all monoamine transporters (Wall et al., 1995). 5-HT and MPP+ differ in theirK m value for the hSERT by a factor of about 25 (0.6 versus 17 μM, respectively) and in their lipophilicity. These differences are the cause of some typical findings, which have been partly discussed previously (Scholze et al., 2000; Sitte et al., 2000) and will be reviewed here because of their relevance for the present findings. Because the cells used in the present experiments do not possess a vesicular storage mechanism, accumulated 5-HT will leave the cytoplasm by diffusion, but is partly subject to reuptake because of its high ...
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Sigma-Aldrich offers abstracts and full-text articles by [Justin R Nickell, Guangrong Zheng, Agripina G Deaciuc, Peter A Crooks, Linda P Dwoskin].
Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. of NFATp in articular cartilage cells leads to increased appearance of cartilage markers whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype. Hence NFATp is normally a repressor of cartilage cell development and differentiation and in addition gets the properties of the tumor suppressor. mutation is normally supplementary to inactivation from the BMP5 gene 47 whereas mutations from the GDF5 gene take into account limb modifications in mice 67. Indian Hedgehog is normally portrayed in prehypertrophic chondrocytes where it settings the pace of hypertrophic differentiation in part through inducing the manifestation of a second transmission PTHrP in the perichondrium. PTHrP?/? mice have defects AG-014699 in formation of hypertrophic cartilage 54 57. Indeed we found no evidence that NFATp directly controlled the ...
Mast cells donate to allergy through IgE-dependent activation the high-affinity IgE receptor FcεRI. receptor gain-of-function human mast cell line HMC-1. Unlike MS4A2 MS4A2trunc did not traffic to the cytoplasmic membrane but instead was associated with the nuclear membrane. Overexpression of MS4A2trunc induced human lung mast cell death and profoundly inhibited HMC-1 cell proliferation by inducing G2-phase cell cycle arrest and apoptosis. Thus we have identified a novel splice variant of MS4A2 that might be important in the regulation of human mast cell proliferation and survival. This finding demonstrates that the MS4A2 gene has multiple roles extending beyond the rules of acute sensitive reactions. By understanding the systems regulating its function it could be feasible to induce its manifestation in mast cells cells had been then transformed using the MS4A2 clones and plated from agar plates including 100 μg/ml ampicillin with 100 μl of IPTG and 20 μl of X-galactose added. Transformed ...
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2. Brain Vesicular Monoamine Transporter and Apoptosis: Perspectives on Development and Neurodegeneration (L a Stankovski, Patricia Gaspar and Olivier Cases)pp. 21- ...
The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).[supplied by OMIM, Mar 2008 ...
Introduction: The most abundant neuroendocrine (NE) cell population of the human oxyntic mucosa is the enterochromaffin-like (ECL) cells, followed by ghrelin, somatostatin and serotonin cells, respectively. All types of ECL cell carcinoids (ECL-CCs) contain serotonin cells but in a varying frequency. Hitherto, only foci of ECL and ghrelin cell hyperplasia have been described in the peritumorous mucosa of types I and II ECL-CCs. It is established that hypergastrinaemia can cause ECL cell hyperplasia but it does not affect serotonin cells. The vesicular monoamine transporter 2 (VMAT 2) is used as an immunohistochemical marker for ECL cells ...
This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canadas national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc. ...
Tamminga CA, Nemeroff CB, Blakely RD, Brady L, Carter CS, Davis KL, Dingledine R, Gorman JM, Grigoriadis DE, Henderson DC, B Innis RB, Killen J, Laughren TP, McDonald WM, M Murphy GM Jr, Paul SM, Rudorfer MV, Sausville E, Schatzberg AF, Scolnick EM, Suppes T; ; , PubMed Europe PMC Scholia ...
My last neurologist appointment was with me my doctors fellow who told that me nasal congestion is not a common side effect of Tetrabenazine. Mice for unjustly taking the Terbutaline and others effective product ehrlichiosis to effective reply. I tried dangerous foreign substance but still got the swelling of the face, fingers, feet, or aga
To analyze the correlation between decline rate of 18F-FP-(+)-DTBZ uptake and clinical severity, and access the feasibility of 18F-DTBZ PET imaging as an in vivo biomarker to monitor neurodegeneration in ...
TY - JOUR. T1 - Vesicular nucleotide transporter (VNUT). T2 - appearance of an actress on the stage of purinergic signaling. AU - Moriyama, Yoshinori. AU - Hiasa, Miki. AU - Sakamoto, Shohei. AU - Omote, Hiroshi. AU - Nomura, Masatoshi. PY - 2017/9/1. Y1 - 2017/9/1. N2 - Vesicular storage of ATP is one of the processes initiating purinergic chemical transmission. Although an active transport mechanism was postulated to be involved in the processes, a transporter(s) responsible for the vesicular storage of ATP remained unidentified for some time. In 2008, SLC17A9, the last identified member of the solute carrier 17 type I inorganic phosphate transporter family, was found to encode the vesicular nucleotide transporter (VNUT) that is responsible for the vesicular storage of ATP. VNUT transports various nucleotides in a membrane potential-dependent fashion and is expressed in the various ATP-secreting cells. Mice with knockout of the VNUT gene lose vesicular storage and release of ATP from neurons ...
The God gene hypothesis proposes that human spirituality is influenced by heredity and that a specific gene, called vesicular monoamine transporter 2 (VMAT2), predisposes humans towards spiritual or mystic experiences. The idea has been proposed by geneticist Dean Hamer in the 2004 book called The God Gene: How Faith is Hardwired into our Genes. The God gene hypothesis is based on a combination of behavioral genetic, neurobiological and psychological studies. The major arguments of the hypothesis are: (1) spirituality can be quantified by psychometric measurements; (2) the underlying tendency to spirituality is partially heritable; (3) part of this heritability can be attributed to the gene VMAT2; (4) this gene acts by altering monoamine levels; and (5) spirituality provides an evolutionary advantage by providing individuals with an innate sense of optimism. According to the God Gene hypothesis, spirituality has a genetic component, of which (VMAT2) comprises one component by contributing to ...
SAN DIEGO - June 6, 2016 - Crinetics Pharmaceuticals ("Crinetics"), an innovative therapeutics company focused on specialty endocrine disorders, announced today the addition of Ajay Madan, Ph.D., D.A.B.T. as Vice President, Development.. "We continue to strategically assemble a world-class team with deep expertise in discovering and developing innovative therapeutics," said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. "I am thrilled to be working with such an accomplished drug developer once again and will rely on his expertise as we transform Crinetics into a clinical-stage therapeutics company.". Dr. Madan was most recently Vice President of Preclinical Development at Neurocrine Biosciences. He was responsible for bioanalytical analysis, drug metabolism, pharmacokinetics, toxicology, and clinical pharmacology in support of a number of drug discovery and development programs. He also initiated and led the vesicular monoamine transporter 2 (VMAT2) inhibitor program ...
TY - JOUR. T1 - Brain biogenic amine levels after methanol administration. T2 - Possible mechanism of action of central monoaminergic neurons in discrete areas of brain in Wistar rats. AU - Jeganathan, P. S.. AU - Namasivayam, A.. PY - 1989/1/1. Y1 - 1989/1/1. UR - http://www.scopus.com/inward/record.url?scp=0024396801&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0024396801&partnerID=8YFLogxK. M3 - Article. C2 - 2592039. AN - SCOPUS:0024396801. VL - 33. SP - 151. EP - 156. JO - Indian Journal of Physiology and Pharmacology. JF - Indian Journal of Physiology and Pharmacology. SN - 0019-5499. IS - 3. ER - ...
Tetrabenazine by Sterimax: Tetrabenazine belongs to the class of medications called monoamine depleting agents. It is used to reduce uncontrolled movement that is seen in Huntingtons chorea, tardive dyskinesia, hemiballismus, senile chorea, tic and Tourettes syndrome. This medication works in the brain, interfering with the storage of some of the chemicals that are linked to movement disorders, such as serotonin and dopamine.
Tetrabenazine is intended for Pharmaceuticals applications. All information about Tetrabenazine, racemic mixture is provided in the MSDS. We deliver compounds with high purity levels and a comprehensive Certificate of Analysis. Connect to your member account to consult the documents ...
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Health,... WASHINGTON Dec. 6 /- An advisory committee to the U.... The advisory committees support of tetrabenazine represents animpor...While the FDA is not required to follow the advice of its advisorycom...HD is a devastating neurodegenerative disease that causes progressive...,FDA,Advisory,Committee,Votes,Unanimously,to,Recommend,Approval,of,Tetrabenazine,for,Chorea,Associated,With,Huntington,Disease,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Vesicular Neurotransmitter Transport Proteins: A family of neurotransmitter transporter proteins that are INTEGRAL MEMBRANE PROTEINS of the LIPID BILAYER of SECRETORY VESICLES. They are ANTIPORTERS that exchange vesicular PROTONS for cytoplasmic NEUROTRANSMITTER and play an essential role in regulating neurotransmission.
Federal drug regulators gave the go ahead for the drug, tetrabenazine, to help with one of the most prominent symptoms of Huntingtons disease, chorea.
A primary interest of our lab is to understand how nerve cells make and recycle neurotransmitters, the small molecules that they use to communicate with each other. In better defining these processes we hope to achieve our long-term goal of identifying novel sites for treatment of diseases such as epilepsy and Parkinson Disease. In our studies on neurotransmitter metabolism we have focused our efforts on transporters, a functional class of proteins that move neurotransmitters and other small molecules across membranes in cells. Transporters have many characteristics that make them excellent pharmacological targets, and not surprisingly some of the most effective treatments for neuropsychiatric disorders are directed at transporters. We are specifically focusing on two groups of transporters vesicular neurotransmitter transporters that package neurotransmitters into vesicles for release, and glutamine transporters that shuttle glutamine, a precursor for two major neurotransmitters glutamate and ...
Xenazine is used to treat chorea (a movement disorder) that is caused by Huntington disease. Xenazine works in the central nervous system (CNS) to prevent the absorption of certain...
Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula... To see the remainder of this abstract, please download this patent.
그러나, 다른 이론은 monoamine의 정지가 총 민감성을 회복하기 위해 뇌의 monoamine 수용기를 되찾을 수 있게 하기 위해 요구 되는 것이라고 주장한다. 만약 렘 수면이 반복적으로 중단된 사람은 다음 기회에 Rebound sleep 으로 더 긴 렘 수면을 보상 받을 것이다. 그 유일한 치료방법은 일찍 자는 것이다. 특정 신경전달물질의 불균형과 관계 되어 나타나는 우울증의 경우일 때, 예리한 렘 수면 손실은 그 특정 우울증을 야기한다고 주장된다. 그러나 이것은 증명되지 않았다. 화학적 불균형의 가설을 증명할 실험도 알려지지 않았다. 대부분 항 우울증은 monoamine영향으로 인해 선택적으로 렘 수면을 제어한다. 그러나 그 효과는 오랜 기간 지나면 효과가 감소한다. 일부 연구자들은 렘 수면이 조류와 포유류의 생존을 위한 중요 기능을 돕는 것과 같은 복잡한 과정의 ...
But having dopamine floating around inside cells is actually stressful for them. The dopamine is unstable and can damage the cells machinery. Millers team has been studying a protein called VMAT2. It packages dopamine into membrane-clothed bags called vesicles. The vesicles sequester the dopamine in a safe container before it is spritzed outside to do its job of signaling to other brain cells.. Researchers already knew that having inadequate levels of VMAT2 leads to a Parkinsons-like condition in mice. But until this paper, nobody had looked at what happens if mice are forced to make more VMAT2 than usual.. Brain cells from mice with an extra VMAT2 gene take up more dopamine and package it better. Their vesicles are larger. The authors write that they hypothesized that the mice would display increased anxiety-like or mania-like behaviors, but this didnt turn out to be the case.. The mice that make extra VMAT2 were more resistant to MPTP, a toxin that is often used to produce a model of ...
The AVMA Veterinary Medical Assistance Teams are enhancing their training component through the establishment of VMAT U, which debuted during the AVMA Annual
article{f82a7d8f-ab38-4eb1-8665-9a38ec51ce38, abstract = {Background & Aims: Gastrin stimulation of the type 2 cholecystokinin (CCK2) receptor results in ECL cell proliferation and histamine secretion. This report describes the effects of targeted disruption of the CCK2 receptor gene on ECL cell morphology and function. Methods: The ECL cells in the oxyntic mucosa of CCK2 receptor-deficient (knockout [KO]) vs. wild-type (WT) mice were investigated by immunocytochemical and biochemical approaches, as well as by electron microscopy. Results: Immunocytochemistry demonstrates similar numbers (cells per millimeter of horizontal length of mucosa) of pancreastatin- or vesicle monoamine transporter-2 (VMAT-2)-immunoreactive cells in WT mice and KO mice. However, only WT mice harbor histamine-immunoreactive ECL cells. The mucosal histamine content in KO mice (likely originating from mast cells) is only a minute fraction of that present in WT animals. The activity of the histamine forming enzyme, ...
A primary interest of our lab is to understand how nerve cells make and recycle neurotransmitters, the small molecules that they use to communicate with each other. In better defining these processes we hope to achieve our long-term goal of identifying novel sites for treatment of diseases such as epilepsy and Parkinson Disease. In our studies on neurotransmitter metabolism we have focused our efforts on transporters, a functional class of proteins that move neurotransmitters and other small molecules across membranes in cells. Transporters have many characteristics that make them excellent pharmacological targets, and not surprisingly some of the most effective treatments for neuropsychiatric disorders are directed at transporters. We are specifically focusing on two groups of transporters vesicular neurotransmitter transporters that package neurotransmitters into vesicles for release, and glutamine transporters that shuttle glutamine, a precursor for two major neurotransmitters glutamate and ...
Nicotine is a powerful pharmacological agent that has both stimulant and depressant effects on the central nervous system (Henningfield et al., 1991). The very high prevalence of smoking among patients with depression and other psychiatric disorders may be caused by nicotines effect on mood. Major depression is more common among smokers than nonsmokers, further suggesting an important relationship between nicotine dependence and mood disorders. The relationship between nicotine dependence and mood disorders led researchers to consider antidepressants as potential treatments for smoking cessation. Thus far, the most useful anti-depressant evaluated is bupropion.. Much research has been directed toward studies to identify the mechanism of antidepressant activity of bupropion. However, the specific sites that are responsible for its biological activity are still not fully understood. It is well recognized that bupropion exhibits both noradrenergic and dopaminergic activity. Thus, the effectiveness ...
Physiology Test Question - The exocytotic release of hormones stored in secretory vesicles is triggered by a rise in cytoplasmic __________ concentration.
A phase 3 clinical trial of tetrabenazine showed the drug to be effective in the treatment of chorea associated with Huntingtons disease (HD). The results of the study presented at the 129th annual meeting of the American Neurological Association validated the treatment success that has been seen in Europe, Australia, and Canada. In a randomized, double-blind, placebo-controlled study of 84 patients with HD, patients received either tetrabenazine or a placebo for 12 weeks. The objective was to change baseline scores on the Unified Huntingtons Disease Rating Scale, which is used to assess clinical elements. After 12 weeks, the chorea score for the tetrabenazine group had decreased by 5 points, whereas the scores for the placebo group had decreased by only 1.5 points. Tetrabenazine also was proven to be superior to placebo on the Clinical Global Impression Scale, which assesses severity of illness and change in clinical condition. The drugs manufacturer, Prestwick Pharmaceuticals Inc, plans to ...
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Triple reuptake inhibitors (TRIs) are compounds designed to block the serotonin, noradrenaline, and dopamine transporters, enhancing monoaminergic neurotransmission, and are seen as a promising advance in the treatment of neuropsychiatric disorders (Marks et al., 2008). GSK1360707 is a novel TRI that has been shown to be potent and selective, with excellent in vitro and in vivo profiles [see compound 17 in Micheli et al. (2010); for structure, see Teller and Furstner (2011)].. Until recently, GSK1360707 was being developed for the treatment of major depressive disorder. Current therapies for major depressive disorders typically have response rates of 50-65% (Weinmann et al., 2008) and clinically meaningful activity only after 2 to 4 weeks (Montgomery, 1997). It is hypothesized that the blockade of the three monoamine transporters will improve tolerability, speed of onset, response, and remission rates. An effective TRI could reduce the need to use multiple psychoactive medications in individual ...
The localization of dopamine stores and the expression and localization of dopamine (DAT) and vesicular monoamine transporters (VMAT) type-1 and -2 and of dopamine D1-like and D2-like receptor subtypes were investigated in rat submandibular, sublingual, and parotid salivary glands by HPLC with electrochemical detection, as well as immunochemical and immunohistochemical techniques. Male Wistar rats of 2 mo of age were used. The highest dopamine levels were measured in the parotid gland, followed by the submandibular and sublingual glands. Western blot analysis revealed DAT, VMAT-1, VMAT-2, and dopamine receptors immunoreactivity in membrane preparations obtained from the three glands investigated. Immunostaining for dopamine and transporters was developed within striated ducts. Salivary glands processed for dopamine receptors immunohistochemistry developed an immunoreaction primarily in striated and excretory ducts. In the submandibular gland, acinar cells displayed strong immunoreactivity for ...
It has been shown that vitamin C (VC) is transported at synaptic boutons, but how this occurs has not been elucidated. This study investigates the role of the sodium-dependent vitamin C transporter-2 (SVCT2) in transporting VC at the cortical nerve terminal. Immunostaining of cultured mouse superior cervical ganglion cells showed the SVCT2 to be expressed in presynaptic boutons, colocalizing with the vesicular monoamine transporter-2 and the norepinephrine transporter. Immunoblotting of enriched cortical synaptosomes demonstrated that the SVCT2 was enriched in presynaptic fractions, confirming a predominantly presynaptic location. In crude synaptosomes, known inhibitors of SVCT2 inhibited uptake of VC. Furthermore, the kinetic features of VC uptake were consistent with SVCT2-mediated function. VC was also found to efflux from synaptosomes by a mechanism not involving the SVCT2. Indeed, VC efflux was substantially offset by reuptake of VC on the SVCT2. The presence and function of the SVCT2 at ...