Pharmacological and functional characterization of excitatory amino acid mediated cytotoxicity in cerebral cortical neurons

1992 ◽  
Vol 8 (3) ◽  
pp. 93-100 ◽  
Author(s):  
Arne Schousboe ◽  
Aase Frandsen ◽  
P. Krogsgaard-Larsen
2021 ◽  
Author(s):  
Hans Renata ◽  
Emily Shimizu ◽  
Christian Zwick

We report the functional characterization of two iron- and a-ketoglutarate-dependent dioxygenases that are capable of hydroxylating free-standing glutamine at its C3 and C4 position respectively. In particular, the C4 hydroxylase, Q4Ox, catalyzes the reaction with approximately 4,300 total turnover numbers, facilitating synthesis of a solid-phase compatible building block and stereochemical elucidation at the C4 position of the hydroxylated product. This work will enable the development of novel synthetic strategies to prepare useful glutamine derivatives and stimulate further discoveries of new amino acid hydroxylases with distinct substrate specificities.<br>


2021 ◽  
Author(s):  
Hans Renata ◽  
Emily Shimizu ◽  
Christian Zwick

We report the functional characterization of two iron- and a-ketoglutarate-dependent dioxygenases that are capable of hydroxylating free-standing glutamine at its C3 and C4 position respectively. In particular, the C4 hydroxylase, Q4Ox, catalyzes the reaction with approximately 4,300 total turnover numbers, facilitating synthesis of a solid-phase compatible building block and stereochemical elucidation at the C4 position of the hydroxylated product. This work will enable the development of novel synthetic strategies to prepare useful glutamine derivatives and stimulate further discoveries of new amino acid hydroxylases with distinct substrate specificities.<br>


1991 ◽  
Vol 66 (1) ◽  
pp. 293-306 ◽  
Author(s):  
L. J. Larson-Prior ◽  
P. S. Ulinski ◽  
N. T. Slater

1. A preparation of turtle (Chrysemys picta and Pseudemys scripta) brain in which the integrity of the intracortical and geniculocortical pathways in visual cortex are maintained in vitro has been used to differentiate the excitatory amino acid (EAA) receptor subtypes involved in geniculocortical and intracortical synapses. 2. Stimulation of the geniculocortical fibers at subcortical loci produces monosynaptic excitatory postsynaptic potentials (EPSPs) in visual cortical neurons. These EPSPs are blocked by the broad-spectrum EAA receptor antagonist kynurenate (1-2 mM) and the non-N-methyl-D-aspartate (NMDA) antagonist 6, 7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM), but not by the NMDA antagonist D,L-2-amino-5-phosphonovalerate (D,L-AP-5, 100 microM). These results indicate that the geniculocortical EPSP is mediated by EAAs that access principally, if not exclusively, EAA receptors of the non-NMDA subtypes. 3. Stimulation of intracortical fibers evokes compound EPSPs that could be resolved into three components differing in latency to peak. The component with the shortest latency was not affected by any of the EAA-receptor antagonists tested. The second component, of intermediate latency, was blocked by kyurenate and DNQX but not by D,L-AP-5. The component of longest latency was blocked by kynurenate and D,L-AP-5, but not by DNQX. These results indicate that the compound intracortical EPSP is comprised of three pharmacologically distinct components that are mediated by an unknown receptor, by quisqualate/kainate, and by NMDA receptors, respectively. 4. Repetitive stimulation of intracortical pathways at 0.33 Hz produces a dramatic potentiation of the late, D,L-AP-5-sensitive component of the intracortical EPSP. 5. These experiments lead to a hypothesis about the subtypes of EAA receptors that are accessed by the geniculocortical and intracortical pathways within visual cortex.


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