γDGG

gamma-DGG is a competitive AMPA receptor blocker.

In Vitro:gamma-DGG (γ-DGG), a competitive AMPA receptor blocker that blocks less at higher glutamate concentration. At 200-400 μM, gamma-DGG in the bath reduces the miniature EPSC (mEPSC) amplitude by 26±2% (n=5 synapses), and shifts both the mEPSC amplitude distribution and the cumulative probability curve to the left[1]. gamma-DGG (γ-DGG) is the most effective antagonist of the excitatory post-synaptic potentials (e.p.s.p.s). Its action is reversible and not associated with any change in the passive membrane properties of the granule cells or in the apparent reversal potential of the e.p.s.p. Quantal analysis shows that the reduction in the e.p.s.p. paralleled the decrease in quantal size rather than quantal content, confirming a post-synaptic site of the action of gamma-DGG[2].

References:
[1]. Wu XS, et al. The origin of quantal size variation: vesicular glutamate concentration plays a significant role. J Neurosci. 2007 Mar 14;27(11):3046-56. [2]. Crunelli V, et al. Blockade of amino acid-induced depolarizations and inhibition of excitatory post-synaptic potentials in rat dentate gyrus. J Physiol. 1983 Aug;341:627-40.

Glutamate neurotransmission in the cerebellar interposed nuclei: involvement in classically conditioned eyeblinks and neuronal activity.[Pubmed:15331619]

J Neurophysiol. 2005 Jan;93(1):44-52.

The cerebellar interposed nuclei (IN) are critical components of a neural network that controls the expression of classically conditioned eyeblinks. The IN receive 2 major inputs: the massive, gamma-aminobutyric acid (GABA)-mediated input from the Purkinje cells of the cerebellar cortex and the relatively weaker, glutamate-mediated input from collaterals of mossy and climbing fiber cerebellar afferent systems. To elucidate the role of IN glutamate neurotransmission in conditioned response (CR) expression, effects of blocking fast glutamatergic neurotransmission in the IN with gamma-d-glutamylglycine (DGG) on the expression of conditioned eyeblinks and on cerebellar nuclear neuronal activity were examined. Surprisingly, blocking fast glutamate receptors in the IN did not abolish CRs. DGG decreased CR incidence and slightly increased CR latency. In contrast, identical amounts of DGG applied to the cerebellar cortex abolished CRs. Similar to the behavioral effects, DGG had unexpectedly mild effects on IN neurons. At the population level, the baseline firing frequency of IN cells was not affected. After DGG injections, the incidence of excitatory modulation of cell activity in the interstimulus interval decreased but was not abolished. A combined block of fast glutamate and GABA(A) neurotransmission using a mixture of DGG and picrotoxin dramatically reduced CR incidence, increased the firing frequency of all cell types, and virtually abolished all modulation of neuronal activity. These results indicate that fast glutamate neurotransmission in the IN plays only an accessory role both in the expression of behavioral CRs and in the generation of associated neuronal activity in the IN.

Structure-activity relations of dipeptide antagonists of excitatory amino acids.[Pubmed:6392929]

Neuroscience. 1984 Oct;13(2):573-81.

Structure-activity relations of dipeptides related to gamma-D-glutamylglycine have been investigated with respect to the ability of these substances to antagonize depolarizing responses of frog motoneurones in vitro to N-methyl-D-aspartate, kainate and quisqualate. A terminal phosphono group was optimal for N-methyl-D-aspartate antagonist activity in relation to both potency and selectivity. Substances containing a terminal phosphono group were relatively poor antagonists of kainate or quisqualate responses. Terminal carboxylic and sulphonic groups were both effective with respect to kainate and/or quisqualate antagonism. Sulphonic compounds were the more selective in this type of action because of their low affinity for N-methyl-D-aspartate receptors. Optimum chain length for N-methyl-D-aspartate antagonism was between one and two carbon atoms shorter than for optimum kainate/quisqualate antagonist activity. Bulky groups within the N-acylated amino acid moiety generally, but differentially, reduced the ability of the substance to antagonize responses to each of the three agonists. Glutamyl peptides were generally more effective than aspartyl peptides of the same overall chain length. However, the most potent dipeptide (selective for N-methyl-D-aspartate antagonism) was the aspartyl derivative, beta-D-aspartylaminomethyl phosphonate, for which there was no glutamyl equivalent. Other useful substances to emerge from this study include the relatively selective kainate/quisqualate antagonists, gamma-D-glutamylaminomethyl sulphonate and gamma-D-glutamyltaurine. If similar selectivity is shown in other preparations also, these substances may prove preferable to gamma-D-glutamylglycine as antagonists of synaptic excitation mediated by kainate or quisqualate receptors.