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Escitalopram, a selective serotonin reuptake inhibitor (SSRI) used as an antidepressant.
A reuptake inhibitor (RI) is a type of drug known as a reuptake modulator that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.[1]
Most known reuptake inhibitors affect the monoamine neurotransmitters serotonin, norepinephrine (and epinephrine), and dopamine.[1] However, there are also a number of pharmaceuticals and research chemicals that act as reuptake inhibitors for other neurotransmitters such as glutamate,[2] γ-aminobutyric acid (GABA),[3] glycine,[4] adenosine,[5] choline (the precursor of acetylcholine),[6] and the endocannabinoids,[7] among others.[1]
Contents
1Mechanism of action
1.1Active site transporter substrates
1.2Allosteric site transporter substrates
1.3Vesicular transporter substrates
1.4Indirect unknown mechanism
2Types
2.1Typical
2.2Atypical
2.3Plasmalemmal
2.4Vesicular
3See also
4References
Mechanism of action
This section's factual accuracy is disputed. Relevant discussion may be found on Talk:Reuptake inhibitor. Please help to ensure that disputed statements are reliably sourced.(January 2016) (Learn how and when to remove this template message)
Active site transporter substrates
Tiagabine, a selective GABA reuptake inhibitor used as an anticonvulsant in the treatment of epilepsy and seizures.
Standard reuptake inhibitors are believed to act simply as competitive substrates that work by binding directly to the plasmalemma transporter of the neurotransmitter in question.[8][9][10][11] They occupy the transporter in place of the respective neurotransmitter and competitively block it from being transported from the nerve terminal or synapse into the pre-synaptic neuron. With high enough doses, occupation becomes as much as 80–90%. At this level of inhibition, the transporter will be considerably less efficient at removing excess neurotransmitter from the synapse and this causes a substantial increase in the extracellular concentrations of the neurotransmitter and therefore an increase in overall neurotransmission.
Allosteric site transporter substrates
Alternatively, some reuptake inhibitors bind to allosteric sites and inhibit reuptake indirectly and noncompetitively.
Phencyclidine and related drugs such as benocyclidine, tenocyclidine, ketamine, and dizocilpine (MK-801), have been shown to inhibit the reuptake of the monoamine neurotransmitters.[12][13][14] They appear to exert their reuptake inhibition by binding to vaguely characterized allosteric sites on each of the respective monoamine transporters.[15][16][17][18][19] Benztropine, mazindol, and vanoxerine also bind to these sites and have similar properties.[15][19][20] In addition to their high affinity for the main site of the monoamine transporters, several competitive transporter substrates such as cocaine and indatraline have lower affinity for these allosteric sites as well.[17][19][20]
A few of the selective serotonin reuptake inhibitors (SSRIs) such as the dextro-enantiomer of citalopram appear to be allosteric reuptake inhibitors of serotonin.[21][22] Instead of binding to the active site on the serotonin transporter, they bind to an allosteric site, which exerts its effects by causing conformational changes in the transporter protein and thereby modulating the affinity of substrates for the active site.[21] As a result, escitalopram has been marketed as an allosteric serotonin reuptake inhibitor. Notably, this allosteric site may be directly related to the above-mentioned PCP binding sites.[15][20]
Vesicular transporter substrates
Reserpine, a vesicular reuptake inhibitor that was used in the past to deplete serotonin, norepinephrine, and dopamine stores as an antipsychotic and antihypertensive. It was notorious for causing anxiety and depression, and as a result, was replaced by newer, more modern drugs instead.
A second type of reuptake inhibition affects vesicular transport, and blocks the intracellular repackaging of neurotransmitters into cytoplasmic vesicles. In contrast to plasmalemmal reuptake inhibitors, vesicular reuptake inhibitors do not increase the synaptic concentrations of a neurotransmitter, only the cytoplasmic concentrations; unless, that is, they also act as plasmalemmal transporter reversers via phosphorylation of the transporter protein, also known as a releasing agent. Pure vesicular reuptake inhibitors tend to actually lower synaptic neurotransmitter concentrations, as blocking the repackaging of, and storage of the neurotransmitter in question leaves them vulnerable to degradation via enzymes such as monoamine oxidase (MAO) that exist in the cytoplasm. With vesicular transport blocked, neurotransmitter stores quickly become depleted.
Reserpine (Serpasil) is an irreversible inhibitor of the vesicular monoamine transporter 2 (VMAT2), and is a prototypical example of a vesicular reuptake inhibitor.
Indirect unknown mechanism
Hyperforin, the primary active constituent responsible for the therapeutic benefits of extracts of the herb Hypericum perforatum (St. John's Wort), which is used as an antidepressant.
Two of the primary active constituents of the medicinal herb Hypericum perforatum (St. John's Wort) are hyperforin and adhyperforin.[23][24] Hyperforin and adhyperforin are wide-spectrum inhibitors of the reuptake of serotonin, norepinephrine, dopamine, glutamate, GABA, glycine,[25] and choline,[26] and they exert these effects by binding to and activating the transient receptor potential cation channel TRPC6.[24][27] Activation of TRPC6 induces the entry of calcium (Ca2+) and sodium (Na+) into the cell, which causes the effect through unknown mechanism.[27]
^ abcIversen L. (2006). "Neurotransmitter transporters and their impact on the development of psychopharmacology". Br J Pharmacol. 147 (1): S82–88. doi:10.1038/sj.bjp.0706428. PMC 1760736. PMID 16402124.
^West AR, Galloway MP (1997). "Inhibition of glutamate reuptake potentiates endogenous nitric oxide-facilitated dopamine efflux in the rat striatum: an in vivo microdialysis study". Neurosci. Lett. 230 (1): 21–4. doi:10.1016/S0304-3940(97)00465-5. PMID 9259454.
^Pollack MH, Roy-Byrne PP, Van Ameringen M, Snyder H, Brown C, Ondrasik J, Rickels K (2005). "The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study". J Clin Psychiatry. 66 (11): 1401–8. doi:10.4088/JCP.v66n1109. PMID 16420077.
^Alberati D, Moreau JL, Lengyel J, et al. (February 2012). "Glycine reuptake inhibitor RG1678: a pharmacologic characterization of an investigational agent for the treatment of schizophrenia". Neuropharmacology. 62 (2): 1152–61. doi:10.1016/j.neuropharm.2011.11.008. PMID 22138164.
^Boissard CG, Gribkoff VK (1993). "The effects of the adenosine reuptake inhibitor soluflazine on synaptic potentials and population hypoxic depolarizations in area CA1 of rat hippocampus in vitro". Neuropharmacology. 32 (2): 149–55. doi:10.1016/0028-3908(93)90095-K. PMID 8383814.
^Barkhimer TV, Kirchhoff JR, Hudson RA, Messer WS (November 2002). "Evaluation of the inhibition of choline uptake in synaptosomes by capillary electrophoresis with electrochemical detection". Electrophoresis. 23 (21): 3699–704. doi:10.1002/1522-2683(200211)23:21<3699::AID-ELPS3699>3.0.CO;2-E. PMID 12432531.
^Costa B, Siniscalco D, Trovato AE, Comelli F, Sotgiu ML, Colleoni M, Maione S, Rossi F, Giagnoni G (2006). "AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain". Br J Pharmacol. 148 (7): 1022–32. doi:10.1038/sj.bjp.0706798. PMC 1751928. PMID 16770320.
^Barker, Eric L.; Randy D. Blakely (1995). Norepinephrine and serotonin transporters: molecular targets of antidepressant drugs. In: Psychopharmacology: the fourth generation of progress.
^Sur C, Betz H, Schloss P (1998). "Distinct effects of imipramine on 5-hydroxytryptamine uptake mediated by the recombinant rat serotonin transporter SERT1". Journal of Neurochemistry. 70 (6): 2545–2553. doi:10.1046/j.1471-4159.1998.70062545.x. PMID 9603221.
^Ravna AW, Sylte I, Dahl SG (2003). "Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters". J Pharmacol Exp Ther. 307 (1): 34–41. doi:10.1124/jpet.103.054593. PMID 12944499.
^Apparsundaram S, Stockdale DJ, Henningsen RA, Milla ME, Martin RS (2008). "Antidepressants targeting the serotonin reuptake transporter act via a competitive mechanism". J Pharmacol Exp Ther. 327 (3): 982–990. doi:10.1124/jpet.108.142315. PMID 18801947.
^Pechnick RN, Bresee CJ, Poland RE (2006). "The role of antagonism of NMDA receptor-mediated neurotransmission and inhibition of the dopamine reuptake in the neuroendocrine effects of phencyclidine". Life Sci. 78 (17): 2006–11. doi:10.1016/j.lfs.2005.09.018. PMID 16288927.
^Nishimura M, Sato K, Okada T, Yoshiya I, Schloss P, Shimada S, Tohyama M (1998). "Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells". Anesthesiology. 88 (3): 768–74. doi:10.1097/00000542-199803000-00029. PMID 9523822.
^Nishimura M, Sato K, Okada T, Schloss P, Shimada S, Tohyama M (1998). "MK-801 blocks monoamine transporters expressed in HEK cells". FEBS Lett. 423 (3): 376–380. doi:10.1016/S0014-5793(98)00126-4. PMID 9515743.
^ abcAkunne HC, Reid AA, Thurkauf A, Jacobson AE, de Costa BR, Rice KC, Heyes MP, Rothman RB (1991). "[3H]1-[2-(2-thienyl)cyclohexyl]piperidine labels two high-affinity binding sites in human cortex: further evidence for phencyclidine binding sites associated with the biogenic amine reuptake complex". Synapse. 8 (4): 289–300. doi:10.1002/syn.890080407. PMID 1833849.
^Rothman RB, Reid AA, Monn JA, Jacobson AE, Rice KC (1989). "The psychotomimetic drug phencyclidine labels two high affinity binding sites in guinea pig brain: evidence for N-methyl-D-aspartate-coupled and dopamine reuptake carrier-associated phencyclidine binding sites". Mol. Pharmacol. 36 (6): 887–896. PMID 2557536.
^ abGoodman CB, Thomas DN, Pert A, Emilien B, Cadet JL, Carroll FI, Blough BE, Mascarella SW, Rogawski MA, Subramaniam S, et al. (1994). "RTI-4793-14, a new ligand with high affinity and selectivity for the (+)-MK801-insensitive [3H]1-]1-(2-thienyl)cyclohexyl]piperidine binding site (PCP site 2) of guinea pig brain". Synapse. 16 (1): 59–65. doi:10.1002/syn.890160107. PMID 8134901.
^Rothman RB. (1994). "PCP site 2: a high affinity MK-801-insensitive phencyclidine binding site". Neurotoxicol Teratol. 16 (4): 343–353. doi:10.1016/0892-0362(94)90022-1. PMID 7968938.
^ abcRothman RB, Silverthorn ML, Baumann MH, Goodman CB, Cadet JL, Matecka D, Rice KC, Carroll FI, Wang JB, Uhl GR, et al. (1995). "Studies of the biogenic amine transporters. VI. Characterization of a novel cocaine binding site, identified with [125I]RTI-55, in membranes prepared from whole rat brain minus caudate". J Pharmacol Exp Ther. 274 (1): 385–395. PMID 7616423.
^ abcRothman RB, Cadet JL, Akunne HC, Silverthorn ML, Baumann MH, Carroll FI, Rice KC, de Costa BR, Partilla JS, Wang JB, et al. (1994). "Studies of the biogenic amine transporters. IV. Demonstration of a multiplicity of binding sites in rat caudate membranes for the cocaine analog [125I]RTI-55". J Pharmacol Exp Ther. 270 (1): 296–309. PMID 8035327.
^ abChen F, Larsen MB, Sánchez C, Wiborg O (2005). "The S-enantiomer of R,S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors". Eur. Neuropsychopharmacol. 15 (2): 193–198. doi:10.1016/j.euroneuro.2004.08.008. PMID 15695064.
^Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N (2007). "Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies". Int J Neuropsychopharmacol. 10 (1): 31–40. doi:10.1017/S1461145705006462. PMID 16448580.
^Müller WE, Singer A, Wonnemann M (2001). "Hyperforin – antidepressant activity by a novel mechanism of action". Pharmacopsychiatry. 34 Suppl 1: S98–102. doi:10.1055/s-2001-15512. PMID 11518085.
^ abChatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sci. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.
^Marsh WL, Davies JA (October 2002). "The involvement of sodium and calcium ions in the release of amino acid neurotransmitters from mouse cortical slices elicited by hyperforin". Life Sciences. 71 (22): 2645–55. doi:10.1016/S0024-3205(02)02104-5. PMID 12354583.
^Buchholzer ML, Dvorak C, Chatterjee SS, Klein J (May 2002). "Dual modulation of striatal acetylcholine release by hyperforin, a constituent of St. John's wort". The Journal of Pharmacology and Experimental Therapeutics. 301 (2): 714–9. doi:10.1124/jpet.301.2.714. PMID 11961077.
^ abLeuner K, Kazanski V, Müller M, et al. (December 2007). "Hyperforin – a key constituent of St. John's wort specifically activates TRPC6 channels". The FASEB Journal. 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455.
v
t
e
Pharmacomodulation
Types
♦ Enzyme: Inducer
Inhibitor
♦ Ion channel: Opener
Blocker
♦ Receptor: Agonist
Partial agonist
Antagonist
Inverse agonist
Positive allosteric modulator (PAM)
Negative allosteric modulator (NAM)
♦ Transporter [Reuptake vs Efflux]: Enhancer (RE)
Inhibitor (RI)
Releaser (RA)
♦ Miscellaneous: Precursor
Cofactor
Classes
Enzyme
see Enzyme inhibition
Ion channel
See Ion channel modulators
Receptor & transporter
BA/M
Adrenergic
Adrenergic receptor agonist (α
β (1
2))
Adrenergic receptor antagonist (α (1
2)
β)
Norepinephrine reuptake inhibitor (NRI)
Dopaminergic
Dopamine receptor agonist
Dopamine receptor antagonist
Dopamine reuptake inhibitor (DRI)
Histaminergic
Histamine receptor agonist
Histamine receptor antagonist (H1
H2
H3)
Serotonergic
Serotonin receptor agonist
Serotonin receptor antagonist (5-HT3)
Serotonin reuptake inhibitor (SRI)
AA
GABAergic
GABA receptor agonist
GABA receptor antagonist
GABA reuptake inhibitor (GRI)
Glutamatergic
Glutamate receptor agonist (AMPA)
Glutamate receptor antagonist (NMDA)
Glutamate reuptake inhibitor
Cholinergic
Acetylcholine receptor agonist (Muscarinic
Nicotinic)
Acetylcholine receptor antagonist (Muscarinic
Nicotinic (Ganglionic
Muscular))
Cannabinoidergic
Cannabinoid receptor agonist
Cannabinoid receptor antagonist
Endocannabinoid enhancer (eCBE)
Endocannabinoid reuptake inhibitor (eCBRI)
Opioidergic
Opioid modulator
Opioid receptor agonist
Opioid receptor antagonist
Enkephalinase inhibitor
Other
Adenosine reuptake inhibitor (AdoRI)
Angiotensin II receptor antagonist
Endothelin receptor antagonist
NK1 receptor antagonist
Vasopressin receptor antagonist
Miscellaneous
Cofactor (see Enzyme cofactors)
Precursor (see Amino acids)
UpToDate Contents
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1. 月経前症候群および月経前不快気分障害の疫学および病因 epidemiology and pathogenesis of premenstrual syndrome and premenstrual dysphoric disorder
Neuronal release and successful astrocyte uptake of aminoacidergic neurotransmitters after spinal cord injury in lampreys.
Fernández-López B1, Valle-Maroto SM, Barreiro-Iglesias A, Rodicio MC.Author information 1Department of Cell Biology and Ecology, CIBUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.AbstractIn contrast to mammals, the spinal cord of lampreys spontaneously recovers from a complete spinal cord injury (SCI). Understanding the differences between lampreys and mammals in their response to SCI could provide valuable information to propose new therapies. Unique properties of the astrocytes of lampreys probably contribute to the success of spinal cord regeneration. The main aim of our study was to investigate, in the sea lamprey, the release of aminoacidergic neurotransmitters and the subsequent astrocyte uptake of these neurotransmitters during the first week following a complete SCI by detecting glutamate, GABA, glycine, Hu and cytokeratin immunoreactivities. This is the first time that aminoacidergic neurotransmitter release from neurons and the subsequent astrocytic response after SCI are analysed by immunocytochemistry in any vertebrate. Spinal injury caused the immediate loss of glutamate, GABA and glycine immunoreactivities in neurons close to the lesion site (except for the cerebrospinal fluid-contacting GABA cells). Only after SCI, astrocytes showed glutamate, GABA and glycine immunoreactivity. Treatment with an inhibitor of glutamate transporters (DL-TBOA) showed that neuronal glutamate was actively transported into astrocytes after SCI. Moreover, after SCI, a massive accumulation of inhibitory neurotransmitters around some reticulospinal axons was observed. Presence of GABA accumulation significantly correlated with a higher survival ability of these neurons. Our data show that, in contrast to mammals, astrocytes of lampreys have a high capacity to actively uptake glutamate after SCI. GABA may play a protective role that could explain the higher regenerative and survival ability of specific descending neurons of lampreys. GLIA 2014.
Glia.Glia.2014 Apr 15. doi: 10.1002/glia.22678. [Epub ahead of print]
In contrast to mammals, the spinal cord of lampreys spontaneously recovers from a complete spinal cord injury (SCI). Understanding the differences between lampreys and mammals in their response to SCI could provide valuable information to propose new therapies. Unique properties of the astrocytes of
Cooperation of taurine uptake and dopamine D1 receptor activation facilitates the induction of protein synthesis-dependent late LTP.
Suárez LM1, Bustamante J2, Orensanz LM3, Martín del Río R4, Solís JM5.Author information 1Instituto Cajal CSIC, Ave. Doctor Arce 37, Madrid 28002, Spain; Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: luz.m.suarez@cajal.csic.es.2Dpto. de Fisiología, Facultad Medicina, UCM, IRYCIS, Madrid 28040, Spain. Electronic address: jubustam@med.ucm.es.3Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: luis.m.orensanz@hrc.es.4Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: rafael.martin@hrc.es.5Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: jose.m.solis@hrc.es.AbstractCo-activation of NMDA and dopamine receptors is required for the induction of the late phase of LTP (L-LTP) that is dependent on new protein synthesis. Other neuromodulatory substances may also contribute to this process. Here, we examined whether taurine is one of the neuromodulators contributing to L-LTP induction, since it is known that taurine uptake induces a long-lasting synaptic potentiation dependent on protein synthesis, and taurine uptake inhibition blocks L-LTP induced by tetanization. Experiments were conducted using rat hippocampal slices where field synaptic potentials were evoked and recorded in CA3-CA1 synapses. Taurine (1 mM) applied 10 min before a high frequency stimulation (HFS) train converted a transitory early-LTP (E-LTP) into an L-LTP dependent on protein synthesis. This taurine effect was blocked by a taurine uptake inhibitor. A facilitation of L-LTP induction was also obtained by pre-application of SKF38393, a D1/D5 dopamine receptor (D1R) agonist. In this case, LTP facilitation was not affected by the taurine uptake inhibitor. Nevertheless, when taurine and SKF38393 were simultaneously pre-applied at a concentration that individually did not modify E-LTP, they produced a synergistic mechanism that facilitated the induction of L-LTP with a sole HFS train. This facilitation of L-LTP was blocked by inhibiting either taurine uptake or D1R activation. Taurine and SKF38393 activated different signaling pathways to transform E-LTP into L-LTP. Taurine-induced L-LTP facilitation required MAPK activation, while D1R-agonist-induced facilitation depended mainly on PKA activation and partially on MAPK activation. On the other hand, the synergistic mechanisms induced by the cooperative action of taurine and SKF38393 were impaired by inhibitors against MAPK, PKA and PI3-K. This pharmacological profile resembles that displayed by L-LTP induced by three HFS trains at 10-min intervals. These results indicate that taurine uptake is necessary and cooperates with other neurotransmitter systems in the induction of L-LTP.
Neuropharmacology.Neuropharmacology.2014 Apr;79:101-11. doi: 10.1016/j.neuropharm.2013.10.035. Epub 2013 Nov 10.
Co-activation of NMDA and dopamine receptors is required for the induction of the late phase of LTP (L-LTP) that is dependent on new protein synthesis. Other neuromodulatory substances may also contribute to this process. Here, we examined whether taurine is one of the neuromodulators contributing t
Characteristics of endogenous γ-aminobutyric acid (GABA) in human platelets: functional studies of a novel collagen glycoprotein VI inhibitor.
Lin KH1, Lu WJ, Wang SH, Fong TH, Chou DS, Chang CC, Chang NC, Chiang YC, Huang SY, Sheu JR.Author information 1Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Rd., Shih-Lin, Taipei, 11101, Taiwan.Abstractgamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and it also appears in peripheral tissues. Platelets are anuclear blood cells that play a central role in hemostatic processes. Although platelets possess a GABA uptake system, the functional activity of GABA in platelets has remained unclear. We determined that GABA is abundantly distributed in the platelets at a concentration of approximately 1.03 ng/106 cells. GABA (0.5 μM) specifically inhibited collagen-induced platelet activation accompanied by [Ca2+]i mobilization, phospholipase Cγ2, protein kinase C, Akt phosphorylation, and hydroxyl radical formation. In addition, GABA interfered with fluorescein isothiocyanate-collagen binding to platelet membranes and produced a concentration-dependent shift in the collagen concentration-response curve and a Schild plot slope of -0.96 ± 0.11, indicating competitive inhibition. Platelet activation induced by convulxin, a glycoprotein VI agonist, was inhibited by GABA, whereas activation induced by the integrin α2β1 agonist, aggretin, was not. Immunoprecipitation and surface plasmon resonance revealed that GABA binds directly to glycoprotein VI in human platelets with equilibrium dissociation (binding) constant (K D) of 41.4 nM. The closure time of whole blood and the occlusion time of platelet plug formation were significantly prolonged by GABA in vivo. In this study, GABA is a specific inhibitor of collagen glycoprotein VI and may be involved in an endogenous negative feedback mechanism for platelet activation. Thus, GABA may represent a potential target for the development of novel interventions for the treatment of cardiovascular diseases associated with platelet activation, such as stroke and myocardial infarction.
Journal of molecular medicine (Berlin, Germany).J Mol Med (Berl).2014 Mar 14. [Epub ahead of print]
gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and it also appears in peripheral tissues. Platelets are anuclear blood cells that play a central role in hemostatic processes. Although platelets possess a GABA uptake system, the functional activ
… L-glutamate (Glu) has been thought to be an excitatory amino acid neurotransmitter in the mammalian central nervous system. … In addition, [3H]Glu uptake was also seen in a temperature- and sodium-dependent manner with pharmacological profiles similar to those for brain GluTs in osteoblasts. … Glu markedly inhibited osteoclastogenesis in a manner sensitive to the antiporter inhibitor. …
Regulated Expression and Function of the Somatodendritic Catecholamine Neurotransmitter Transporters
Kitayama Shigeo,Sogawa Chiharu
Journal of pharmacological sciences 99(2), 121-127, 2005-10-20
… Termination of neurotransmission at catecholaminergic synapses is well documented by the transporters for dopamine and norepinephrine, members of the Na+/Cl－-dependent neurotransmitter transporter family, which accumulates released transmitters within their nerve endings, respectively. … Recent findings of the transporter function as an ion channel and/or its reverse transport property provide a clue to identify the role of these transporters in the somatodendrites and their consequential interaction with uptake inhibitors. …
Glutamate Transport and Storage in Synaptic Vesicles
Ozkan Eric D.,Ueda Tetsufumi
The Japanese journal of pharmacology 77(1), 1-10, 1998-05-01
… In particular, glutamate is the most common excitatory neurotransmitter in the vertebrate central nervous system. … As such, the mechanism by which glutamate is diverted from its normal metabolic activities toward its role as a neurotransmitter has, in recent years, been systematically investigated. … Glutamate accumulation is accomplished by virtue of a glutamate uptake system present in the synaptic vesicle membrane. …