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Full-Text Articles in Medicine and Health Sciences
Constitutive Ion Fluxes And Substrate Binding Domains Of Human Glutamate Transporters, Robert J. Vandenberg, Jeffrey L. Arriza, Susan G. Amara, Michael Kavanaugh
Constitutive Ion Fluxes And Substrate Binding Domains Of Human Glutamate Transporters, Robert J. Vandenberg, Jeffrey L. Arriza, Susan G. Amara, Michael Kavanaugh
Biomedical and Pharmaceutical Sciences Faculty Publications
Application of L-glutamate activates ionic currents in voltage-clamped Xenopus oocytes expressing cloned human excitatory amino acid transporters (EAATs). However, even in the absence of L-glutamate, the membrane conductance of oocytes expressing EAAT1 was significantly increased relative to oocytes expressing EAAT2 or control oocytes. Whereas transport mediated by EAAT2 is blocked by the non-transported competitive glutamate analog kainate (K = 14 μM), EAAT1 is relatively insensitive (K > 3 mM). Substitution of a block of 76 residues from EAAT2 into EAAT1, in which 18 residues varied from EAAT1, conferred high affinity kainate binding to EAAT1, and application of kainate to …
Differential Modulation Of Human Glutamate Transporter Subtypes By Arachidonic Acid, Noa Zerangue, Jeffrey L. Arriza, Susan G. Amara, Michael Kavanaugh
Differential Modulation Of Human Glutamate Transporter Subtypes By Arachidonic Acid, Noa Zerangue, Jeffrey L. Arriza, Susan G. Amara, Michael Kavanaugh
Biomedical and Pharmaceutical Sciences Faculty Publications
Arachidonic acid has been proposed to be a messenger molecule released following synaptic activation of glutamate receptors and during ischemia. Here we demonstrate that micromolar levels of arachidonic acid inhibit glutamate uptake mediated by EAAT1, a human excitatory amino acid transporter widely expressed in brain and cerebellum, by reducing the maximal transport rate approximately 30%. In contrast, arachidonic acid increased transport mediated by EAAT2, a subtype abundantly expressed in forebrain and midbrain, by causing the apparent affinity for glutamate to increase more than 2-fold. The results demonstrate that the response of different glutamate transporter subtypes to arachidonic acid could influence …
A Family Of Putative Receptor-Adenylate Cyclases From Leishmania Donovani, Marco A. Sanchez, David Zeoli, Elizabeth M. Klamo, Michael Kavanaugh, Scott M. Landfear
A Family Of Putative Receptor-Adenylate Cyclases From Leishmania Donovani, Marco A. Sanchez, David Zeoli, Elizabeth M. Klamo, Michael Kavanaugh, Scott M. Landfear
Biomedical and Pharmaceutical Sciences Faculty Publications
Leishmania parasites are exposed to pronounced changes in their environment during their life cycle as they migrate from the sandfly midgut to the insect proboscis and then into the phagolysosomes of the vertebrate macrophages. The developmental transformations that produce each life cycle stage of the parasite may be signaled in part by binding of environmental ligands to receptors which mediate transduction of extracellular signals. We have identified a family of five clustered genes in Leishmania donovani which may encode signal transduction receptors. The coding regions of two of these genes, designated rac-A and rac-B, have been sequenced and shown …