6729-55-1Relevant articles and documents
Photolysis of a caged, fast-equilibrating glutamate receptor antagonist, MNI-caged γ-D-glutamyl-glycine, to investigate transmitter dynamics and receptor properties at glutamatergic synapses
Palma-Cerda, Francisco,Papageorgiou, George,Barbour, Boris,Auger, Céline,Ogden, David
, (2019/01/04)
Fast uncaging of low affinity competitive receptor antagonists can in principle measure the timing and concentration dependence of transmitter action at receptors during synaptic transmission. Here, we describe the development, synthesis and characterization of MNI-caged γ-D-glutamyl-glycine (γ-DGG), which combines the fast photolysis and hydrolytic stability of nitroindoline cages with the well-characterized fast-equilibrating competitive glutamate receptor antagonist γ-DGG. At climbing fiber-Purkinje cell (CF-PC) synapses MNI-caged-γ-DGG was applied at concentrations up to 5 mM without affecting CF-PC transmission, permitting release of up to 1.5 mM γ-DGG in 1 ms in wide-field flashlamp photolysis. In steady-state conditions, photoreleased γ-DGG at 0.55–1.7 mM inhibited the CF first and second paired EPSCs by on average 30% and 60%, respectively, similar to reported values for bath applied γ-DGG. Photolysis of the L-isomer MNI-caged γ-L-glutamyl-glycine was ineffective. The time-course of receptor activation by synaptically released glutamate was investigated by timed photolysis of MNI-caged-γ-DGG at defined intervals following CF stimulation in the second EPSCs. Photorelease of γ-DGG prior to the stimulus and up to 3 ms after showed strong inhibition similar to steady-state inhibition; in contrast γ-DGG applied by a flash at 3–4 ms post-stimulus produced weaker and variable block, suggesting transmitter-receptor interaction occurs mainly in this time window. The data also show a small and lasting component of inhibition when γ-DGG was released at 4–7 ms post stimulus, near the peak of the CF-PC EPSC, or at 10–11 ms. This indicates that competition for binding and activation of AMPA receptors occurs also during the late phase of the EPSC, due to either delayed transmitter release or persistence of glutamate in the synaptic region. The results presented here first show that MNI-caged-γ-DGG has properties suitable for use as a synaptic probe at high concentration and that its photolysis can resolve timing and extent of transmitter activation of receptors in glutamatergic transmission.
Isolation and identification of urinary β-aspartyl dipeptides and their concentrations in human urine
Tanaka,Nakajima
, p. 617 - 625 (2007/10/05)
β-Aspartyl-methionine, -aspartic acid and -glutamic acid and γ-glutamyl-threonine and -glycine were isolated and identified in human urine by means of ion-exchange chromatography, highvoltage paper electrophoresis, acid hydrolysis and determination of N-terminal amino acids of the isolated compounds, and comparison of their behaviors in paper electrophoresis and chromatography with those of the authentic compounds. The concentrations of acidic β-aspartyl dipeptides in human urine were determined using an amino acid analyzer. Their concentrations were as follows: β-aspartyl-glycine, male, 44.4±8.5, female, 61.4±18.9, child, 83.7±27.1; -alanine, male, 11.0±4.9, female, 20.7±12.0, child, 25.3±9.1; -glutamic acid, male, 10.0±3.7, female, 23.0±8.5, child, 20.4±7.5; -serine, male, 9.9±2.8, female, 13.6±3.8, child, 14.9±4.7; -aspartic acid, male, 4.3±1.0, female, 9.1±2.2, child, 18.4±6.5; -threonine, male, 3.9±0.9, female, 5.8±1.1, child, 13.2±4.9 μmol/g creatinine (mean ± S.D.). The order of the sum of their concentrations tended to be child>female>male. Patients receiving intravenous hyperalimentation also excreted acidic β-aspartyl dipeptides into urine in amounts similar to those in females and in a pattern similar to that observed in healthy persons. This finding indicates that urinary β-aspartyl dipeptides were probably of endogenous origin because oral nutrition was stringently excluded in these patients.
