amino acid receptors


Summary: Cell surface proteins that bind amino acids and trigger changes which influence the behavior of cells. Glutamate receptors are the most common receptors for fast excitatory synaptic transmission in the vertebrate central nervous system, and GAMMA-AMINOBUTYRIC ACID and glycine receptors are the most common receptors for fast inhibition.

Top Publications

  1. Finger T, Bryant B, Kalinoski D, Teeter J, Bottger B, Grosvenor W, et al. Differential localization of putative amino acid receptors in taste buds of the channel catfish, Ictalurus punctatus. J Comp Neurol. 1996;373:129-38 pubmed
    ..In addition, PHA-E binds to the apices of solitary chemoreceptor cells in the epithelium, indicating that this independent chemoreceptor system may utilize some receptor sites similar to those in taste buds...
  2. Milburn M, Prive G, Milligan D, Scott W, Yeh J, Jancarik J, et al. Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand. Science. 1991;254:1342-7 pubmed
    ..The structures of the two forms of this protein provide a step toward understanding the mechanisms of transmembrane signaling. ..
  3. Chervitz S, Falke J. Molecular mechanism of transmembrane signaling by the aspartate receptor: a model. Proc Natl Acad Sci U S A. 1996;93:2545-50 pubmed
    ..Together, these approaches provide evidence that aspartate binding triggers a "swinging-piston" displacement of the second membrane-spanning helix, which is proposed to communicate the signal across the bilayer. ..
  4. Madden C, Morrison S. Excitatory amino acid receptors in the dorsomedial hypothalamus mediate prostaglandin-evoked thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2004;286:R320-5 pubmed
    ..These results demonstrate that activation of excitatory amino acid receptors within the DMH is necessary for the thermogenic, metabolic, and cardiovascular responses evoked by ..
  5. Hornby P. Receptors and transmission in the brain-gut axis. II. Excitatory amino acid receptors in the brain-gut axis. Am J Physiol Gastrointest Liver Physiol. 2001;280:G1055-60 pubmed
    ..The emphasis of this themes article is on the potential therapeutic benefits afforded by modulation of these receptors at the site of the dorsal vagal complex...
  6. Milligan D, Koshland D. Site-directed cross-linking. Establishing the dimeric structure of the aspartate receptor of bacterial chemotaxis. J Biol Chem. 1988;263:6268-75 pubmed
    ..Binding of aspartate does not change the oligomeric structure of the receptor, indicating that transmembrane signaling occurs within an oligomeric receptor of constant size. ..
  7. Danielson M, Biemann H, Koshland D, Falke J. Attractant- and disulfide-induced conformational changes in the ligand binding domain of the chemotaxis aspartate receptor: a 19F NMR study. Biochemistry. 1994;33:6100-9 pubmed
    ..It would thus appear that the transmembrane signal is transmitted through this helix.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  8. Kim K, Yokota H, Kim S. Four-helical-bundle structure of the cytoplasmic domain of a serine chemotaxis receptor. Nature. 1999;400:787-92 pubmed
    ..Two of these domains form a long, supercoiled, four-helical bundle in the cytoplasmic portion of the receptor. ..
  9. Magnuson D, Knudsen B, Geiger J, Brownstone R, Nath A. Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol. 1995;37:373-80 pubmed
    ..These results suggest that Tat, released from HIV-1-infected cells, may be an important mediator of neurotoxicity observed in HIV-1 encephalopathy. ..

More Information


  1. Urban M, Coutinho S, Gebhart G. Involvement of excitatory amino acid receptors and nitric oxide in the rostral ventromedial medulla in modulating secondary hyperalgesia produced by mustard oil. Pain. 1999;81:45-55 pubmed
    ..The current study was designed to examine a potential role for excitatory amino acid receptors and nitric oxide in the RVM in modulating this hyperalgesia...
  2. Hyson R. Transneuronal regulation of ribosomes after blockade of ionotropic excitatory amino acid receptors. Brain Res. 1997;749:61-70 pubmed
    ..This was true even though CNQX eliminated driven postsynaptic potentials. These data suggest that ionotropic glutamate receptors are not necessary for the activity-dependent regulation of ribosomes in NM neurons. ..
  3. Michel W, Derbidge D. Evidence of distinct amino acid and bile salt receptors in the olfactory system of the zebrafish, Danio rerio. Brain Res. 1997;764:179-87 pubmed
    ..Presumably, the differences in the extent of partial adaptation are due to differences in the transduction cascades activated or the distribution of odorant receptors on individual olfactory receptor neurons. ..
  4. Bray D, Levin M, Morton Firth C. Receptor clustering as a cellular mechanism to control sensitivity. Nature. 1998;393:85-8 pubmed
    ..A mechanism of this kind can account quantitatively for the sensitivity and response range of E. coli to aspartate. ..
  5. Corner M, Baker R, van Pelt J, Wolters P. Compensatory physiological responses to chronic blockade of amino acid receptors during early development in spontaneously active organotypic cerebral cortex explants cultured in vitro. Prog Brain Res. 2005;147:231-48 pubmed
    ..EEG delta and beta frequency ranges, respectively) even when network bursting tendencies became greatly reduced in favor of tonic firing. ..
  6. Moe G, Bollag G, Koshland D. Transmembrane signaling by a chimera of the Escherichia coli aspartate receptor and the human insulin receptor. Proc Natl Acad Sci U S A. 1989;86:5683-7 pubmed
    ..These results indicate that features of the signaling mechanisms used by these diverse receptors are conserved, but that interesting changes in the protein properties are caused by differences in the neighboring domains. ..
  7. Hales T, Lambert J. The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones. Br J Pharmacol. 1991;104:619-28 pubmed
    ..84-16.8 microM) dose-dependently potentiated strychnine-sensitive currents evoked by glycine (100 microM) in murine spinal neurones. 8. The relevance of the present results to the general anaesthetic action of propofol is discussed. ..
  8. Chen Z, Travers J. Inactivation of amino acid receptors in medullary reticular formation modulates and suppresses ingestion and rejection responses in the awake rat. Am J Physiol Regul Integr Comp Physiol. 2003;285:R68-83 pubmed
    ..responses is poorly understood, studies of fictive mastication suggest that both excitatory and inhibitory amino acid receptors play important roles in the generation of these ororhythmic behaviors...
  9. Verberne A, Beart P, Louis W. Excitatory amino acid receptors in the caudal ventrolateral medulla mediate a vagal cardiopulmonary reflex in the rat. Exp Brain Res. 1989;78:185-92 pubmed
    ..These findings support the hypothesis that the CVLM is an important medullary locus mediating cardiovascular reflex integration and that an EAA synapse in the CVLM is important in the cardiopulmonary reflex arc. ..
  10. Biemann H, Koshland D. Aspartate receptors of Escherichia coli and Salmonella typhimurium bind ligand with negative and half-of-the-sites cooperativity. Biochemistry. 1994;33:629-34 pubmed
    ..Comparison of the X-ray crystal structure of the ligand binding domain with and without bound aspartate revealed ligand-induced conformational changes that explain the two examples of negative cooperativity. ..
  11. Crestani C, Busnardo C, Tavares R, Alves F, Correa F. Involvement of hypothalamic paraventricular nucleus non-N-methyl-D-aspartate receptors in the pressor response to noradrenaline microinjected into the bed nucleus of the stria terminalis of unanesthetized rats. Eur J Neurosci. 2009;29:2166-76 pubmed publisher
    ..They also suggest that a glutamatergic neurotransmission through non-NMDA glutamate receptors in the PVN mediates the response. ..
  12. Winston S, Mehan R, Falke J. Evidence that the adaptation region of the aspartate receptor is a dynamic four-helix bundle: cysteine and disulfide scanning studies. Biochemistry. 2005;44:12655-66 pubmed
    ..A mechanistic model is proposed in which a signal is transmitted through the adaptation subdomain by a change in supercoiling of the four-helix bundle. ..
  13. Stasi K, Mitsacos A, Triarhou L, Kouvelas E. Cerebellar grafts partially reverse amino acid receptor changes observed in the cerebellum of mice with hereditary ataxia: quantitative autoradiographic studies. Cell Transplant. 1997;6:347-59 pubmed
    ..Such changes in GABA(A) receptors suggest a significant, albeit partial, normalizing trend of cerebellar grafts on the state of postsynaptic supersensitive receptors in the host cerebellar nuclei. ..
  14. Irieda H, Homma M, Homma M, Kawagishi I. Control of chemotactic signal gain via modulation of a pre-formed receptor array. J Biol Chem. 2006;281:23880-6 pubmed
    ..These results suggest that receptor covalent modification controls signal gain by altering the arrangement or packing of receptor dimers in a pre-formed cluster. ..
  15. Stross C, Radtke S, Clahsen T, Gerlach C, Volkmer Engert R, Schaper F, et al. Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. J Biol Chem. 2006;281:8458-68 pubmed
    ..However, the inhibition occurs independent of tyrosine motifs within the OSMR. Instead, SOCS3 interacts directly with JAK1 in a stimulation-dependent manner, a mechanism so far only known for SOCS1. ..
  16. Russo A, Koshland D. Separation of signal transduction and adaptation functions of the aspartate receptor in bacterial sensing. Science. 1983;220:1016-20 pubmed
    ..The separation of receptor functions by alteration of primary structure emphasizes that the receptor is directly involved in adaptation and is not solely a device for transmitting a signal across a membrane...
  17. Yeh J, Biemann H, Prive G, Pandit J, Koshland D, Kim S. High-resolution structures of the ligand binding domain of the wild-type bacterial aspartate receptor. J Mol Biol. 1996;262:186-201 pubmed
    ..The conservation of the small angular change in vitro suggests that the inter-subunit rotation may have relevance to the understanding of the mechanism of transmembrane signal transduction in vivo. ..
  18. Bornhorst J, Falke J. Quantitative analysis of aspartate receptor signaling complex reveals that the homogeneous two-state model is inadequate: development of a heterogeneous two-state model. J Mol Biol. 2003;326:1597-614 pubmed
    ..This method suggests that the ratio of receptor dimers to CheA dimers in the assembled complex is 6:1 or less. ..
  19. Gestwicki J, Kiessling L. Inter-receptor communication through arrays of bacterial chemoreceptors. Nature. 2002;415:81-4 pubmed
    ..These results demonstrate that the entire array is involved in sensing. This mode of information exchange has general implications for the processing of signals by cellular receptors. ..
  20. Song D, Choe B, Bae J, Park W, Han I, Ho W, et al. Brain-derived neurotrophic factor rapidly potentiates synaptic transmission through NMDA, but suppresses it through non-NMDA receptors in rat hippocampal neuron. Brain Res. 1998;799:176-9 pubmed
    ..In contrast, BDNF enhanced the EPSCs in the presence of a non-NMDA antagonist CNQX. Our results suggest that BDNF acutely activates synaptic transmission via NMDA, but suppresses it via non-NMDA receptors in the hippocampus. ..
  21. Starrett D, Falke J. Adaptation mechanism of the aspartate receptor: electrostatics of the adaptation subdomain play a key role in modulating kinase activity. Biochemistry. 2005;44:1550-60 pubmed
    ..Overall, this study highlights the importance of electrostatics in signal transduction and regulation of kinase activity by the cytoplasmic domain of the aspartate receptor. ..
  22. Fairman W, Vandenberg R, Arriza J, Kavanaugh M, Amara S. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature. 1995;375:599-603 pubmed
    ..Thus EAAT4 combines the re-uptake of neurotransmitter with a mechanism for increasing chloride permeability, both of which could regulate excitatory neurotransmission. ..
  23. Yu W, Miller R. The mechanism by which NBQX enhances NMDA currents in retinal ganglion cells. Brain Res. 1996;709:184-96 pubmed
    ..Thus the NBQX-induced enhancement phenomenon may reflect a network-selective distribution of NMDA and KA/AMPA receptors among third-order neurons. ..
  24. Jones E, Tighilet B, Tran B, Huntsman M. Nucleus- and cell-specific expression of NMDA and non-NMDA receptor subunits in monkey thalamus. J Comp Neurol. 1998;397:371-93 pubmed
    ..High levels of NR2B are found in astrocytes. Differences in NMDA and non-NMDA receptor profiles will affect functional properties of the thalamic GABAergic and relay cells. ..
  25. Abrahams T, Hornby P, Chen K, DaSilva A, Gillis R. The non-NMDA subtype of excitatory amino acid receptor plays the major role in control of cardiovascular function by the subretrofacial nucleus in cats. J Pharmacol Exp Ther. 1994;270:424-32 pubmed
    ..These data indicate that a non-NMDA EAA receptor plays the major role in control of cardiovascular function by the SRFN. ..
  26. Anderson K, Sandler D. Autoradiography of L-[3H]aspartate binding sites. Life Sci. 1993;52:863-8 pubmed
    ..These results suggest that under these conditions, L-[3H]aspartate specifically labels the sodium-dependent EAA transporter. ..
  27. Singh B, Röhm K. A new subfamily of bacterial glutamate/aspartate receptors. Biol Chem. 2008;389:33-6 pubmed
    ..A database search indicated that AatJ is a member of a distinct subfamily of the family 3 solute-binding proteins with specificity towards glutamate and aspartate...
  28. Lomeli H, Sprengel R, Laurie D, Kohr G, Herb A, Seeburg P, et al. The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett. 1993;315:318-22 pubmed
    ..However, delta-1 gene expression undergoes a pronounced developmental peak, with particularly high mRNA levels in the caudate putamen of late embryonic/early postnatal stages. ..
  29. Vaknin A, Berg H. Osmotic stress mechanically perturbs chemoreceptors in Escherichia coli. Proc Natl Acad Sci U S A. 2006;103:592-6 pubmed
    ..Thus, changes in homodimer spacing and/or orientation appear to initiate osmotactic signaling. ..
  30. Lai R, Bormans A, Draheim R, Wright G, Manson M. The region preceding the C-terminal NWETF pentapeptide modulates baseline activity and aspartate inhibition of Escherichia coli Tar. Biochemistry. 2008;47:13287-95 pubmed publisher
    ..The R505E substitution completely abolishes stimulation of CheA in vitro. Glu-505 may interact electrostatically with Asp-273 to destabilize the "on" signaling state by loosening the four-helix bundle. ..
  31. Dillon G, Welsh D, Waldrop T. Modulation of respiratory reflexes by an excitatory amino acid mechanism in the ventrolateral medulla. Respir Physiol. 1991;85:55-72 pubmed
    ..A more rostral site tonically inhibits respiratory activity and the respiratory responses to chemoreceptor stimulation and more caudal VLM sites may be required for the maintenance of respiratory activity. ..
  32. Milligan D, Koshland D. The amino terminus of the aspartate chemoreceptor is formylmethionine. J Biol Chem. 1990;265:4455-60 pubmed
    ..The stability of the amino-terminal formyl group on the receptor may be a consequence of the membrane localization of the receptor and the dependence of this localization on the membrane transport machinery of the cell. ..
  33. Goff D, Wine L. Glutamate in schizophrenia: clinical and research implications. Schizophr Res. 1997;27:157-68 pubmed
    ..While geriatric patients may be at increased risk for glutamate-mediated neurotoxicity, very little is known about the specific relevance of this model to geriatric patients with schizophrenia. ..
  34. Kretschmer B, Schmidt W, Kostrzewa R, Marschitz Herra M. Amino acids in neurobiology: neuroprotective and neurotoxic aspects of amino acids involved in neurotransmission and neuromodulation -- general introduction. Amino Acids. 2002;23:1-7 pubmed
  35. Soltis R, DiMicco J. Hypothalamic excitatory amino acid receptors mediate stress-induced tachycardia in rats. Am J Physiol. 1992;262:R689-97 pubmed
    ..Thus activity at EAA receptors in the DMH appears to be necessary for the generation of stress-induced changes in heart rate. ..
  36. Carter A, Muller R. Activation of excitatory amino acid receptors cannot alone account for anoxia-induced impairment of protein synthesis in rat hippocampal slices. J Neurochem. 1991;57:888-96 pubmed
    ..These results indicate that the activation of excitatory amino acid receptors cannot alone account for anoxia-induced impairment of protein synthesis in rat hippocampal slices.
  37. Conigrave A, Brown E, Rizzoli R. Dietary protein and bone health: roles of amino acid-sensing receptors in the control of calcium metabolism and bone homeostasis. Annu Rev Nutr. 2008;28:131-55 pubmed publisher
  38. McClay J, van den Oord E. Split genes uncovered through science fusion. Heredity (Edinb). 2005;95:1-2 pubmed
  39. Djordjevic S, Stock A. Chemotaxis receptor recognition by protein methyltransferase CheR. Nat Struct Biol. 1998;5:446-50 pubmed
    ..The structure indicates the basis for the specificity of interaction between the chemoreceptors and CheR and identifies a specific receptor binding motif incorporated in the CheR methyltransferase domain. ..
  40. Bennett M, Balcar V. Forty years of amino acid transmission in the brain. Neurochem Int. 1999;35:269-80 pubmed
    ..The relationship is also explored between these early findings and those of the present era characterised by extensive use of techniques of molecular biology and the development of drugs against targets identified 30 to 40 years ago. ..
  41. Gschwind R, Armbrüster M, Zubrzycki I. NMR detection of intermolecular NH.OP hydrogen bonds between guanidinium protons and bisposphonate moieties in an artificial arginine receptor. J Am Chem Soc. 2004;126:10228-9 pubmed
  42. Sanders D, Koshland D. Receptor interactions through phosphorylation and methylation pathways in bacterial chemotaxis. Proc Natl Acad Sci U S A. 1988;85:8425-9 pubmed
  43. Sal Man N, Gerber D, Shai Y. The composition rather than position of polar residues (QxxS) drives aspartate receptor transmembrane domain dimerization in vivo. Biochemistry. 2004;43:2309-13 pubmed
    ..The results of this study may facilitate a rational modulation of membrane protein function for therapeutic purposes. ..
  44. Bhowmik A, Paimela H, Mustonen H, Kivilaakso E. Roles of cytoskeleton and tyrosine receptor mediated signal transduction in the restitution of isolated guinea pig gastric mucosa. Scand J Gastroenterol. 2002;37:759-64 pubmed
    ..If one of the regulating systems fails, stimulation of the other restores the process. Simultaneous stimulation of both systems has a minor additive effect on both restitution and proliferation. ..
  45. Mehan R, White N, Falke J. Mapping out regions on the surface of the aspartate receptor that are essential for kinase activation. Biochemistry. 2003;42:2952-9 pubmed
  46. Conigrave A, Hampson D. Broad-spectrum amino acid-sensing class C G-protein coupled receptors: molecular mechanisms, physiological significance and options for drug development. Pharmacol Ther. 2010;127:252-60 pubmed publisher
    ..In addition, we consider strategies for the development of new drugs that target these receptors. ..
  47. Coleman M, Bass R, Mehan R, Falke J. Conserved glycine residues in the cytoplasmic domain of the aspartate receptor play essential roles in kinase coupling and on-off switching. Biochemistry. 2005;44:7687-95 pubmed publisher
  48. Kirchner B, Reiher M. Understanding the template preorganization step of an artificial arginine receptor. J Am Chem Soc. 2005;127:8748-56 pubmed
  49. Studdert C, Parkinson J. Insights into the organization and dynamics of bacterial chemoreceptor clusters through in vivo crosslinking studies. Proc Natl Acad Sci U S A. 2005;102:15623-8 pubmed
    ..Moreover, once complete signaling teams have formed, they no longer undergo dynamic exchange of receptor members. ..
  50. Maruyama I, Mikawa Y, Maruyama H. A model for transmembrane signalling by the aspartate receptor based on random-cassette mutagenesis and site-directed disulfide cross-linking. J Mol Biol. 1995;253:530-46 pubmed
    ..Random-cassette mutagenesis and disulfide cross-linking provide powerful strategies for examining the structure and function of transmembrane segments. ..
  51. Wang E, Mowry K, Clegg D, Koshland D. Tandem duplication and multiple functions of a receptor gene in bacterial chemotaxis. J Biol Chem. 1982;257:4673-6 pubmed
    ..coli strains, it is shown that each transmembrane receptor can respond to the small molecule aspartate, to the maltose-protein-chemoeffector complex, and to repellents. ..
  52. Miller A, Falke J. Side chains at the membrane-water interface modulate the signaling state of a transmembrane receptor. Biochemistry. 2004;43:1763-70 pubmed
  53. Krnjevic K. When and why amino acids?. J Physiol. 2010;588:33-44 pubmed publisher
    ..These difficulties were gradually overcome by the application of powerful techniques, such as single channel recording, cloning receptors, as well as new pharmacological tools. ..