Antagonism of Excitatory Amino Acid-Induced and Synaptic Excitation of Spinal Neurones by cis-2,3-Piperidine Dicarboxylate

1981 ◽  
Vol 36 (3) ◽  
pp. 1305-1307 ◽  
Author(s):  
J. Davies ◽  
R. H. Evans ◽  
A. A. Francis ◽  
A. W. Jones ◽  
J. C. Watkins
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Synaptic Excitation ◽  
Spinal Neurones

D-α-Aminoadipate, α,ε-diominopimelic acid and HA-966 as antagonists of amino acid-induced and synaptic excitation of mammalian spinal neurones in vivo

1978 ◽  
Vol 148 (2) ◽  
pp. 543-548 ◽  
Author(s):  
T.J. Biscoe ◽  
J. Davies ◽  
A. Dray ◽  
R.H. Evans ◽  
M.R. Martin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Synaptic Excitation ◽  
Spinal Neurones

Antitussive agents as N-methylaspartate antagonists: further studies

1989 ◽  
Vol 67 (6) ◽  
pp. 561-567 ◽  
Author(s):  
John Church ◽  
Martyn G. Jones ◽  
Stephen N. Davies ◽  
David Lodge
Keyword(s):  
Amino Acid ◽  
Intravenous Injection ◽  
Anticonvulsant Activity ◽  
Excitatory Amino Acid ◽  
Systemic Administration ◽  
Neuroprotective Agents ◽  
Spinal Neurones ◽  
Antitussive Agents ◽  
Relative Potencies

The relative potencies of ketamine and the morphinan derivatives dextrorphan, dextromethorphan, and levorphanol as antagonists of the excitatory actions of N-methylaspartate on rat spinal neurones in vivo were examined, both following their microelectrophoretic administration and, with the exception of levorphanol, after intravenous injection. Applied microelectro-phoretically, dextrorphan was a more potent N-methylaspartate antagonist than ketamine, levorphanol, or dextromethorphan. After systemic administration, however, dextrorphan was rather less potent than ketamine in this respect, whereas dextromethorphan remained less potent than either ketamine or dextrorphan. Noscapine, an antitussive that lacks anticonvulsant activity, failed to reduce selectively responses to N-methylaspartate as did papaverine, an isoquinoline structurally related to noscapine, and triprolidine, an antihistamine commonly found in proprietary cough medicines. The results are discussed with particular reference to the potential of the compounds tested as anticonvulsant and neuroprotective agents in vivo.Key words: dextrorphan, dextromethorphan, antitussive, N-methylaspartate, excitatory amino acid.

D-α-Aminoadipate as a selective antagonist of amino acid-induced and synaptic excitation of mammalian spinal neurones

Nature ◽  
1977 ◽  
Vol 270 (5639) ◽  
pp. 743-745 ◽  
Author(s):  
T. J. BISCOE ◽  
R. H. EVANS ◽  
A. A. FRANCIS ◽  
M. R. MARTIN ◽  
J. C. WATKINS ◽  
...  
Keyword(s):  
Amino Acid ◽  
Selective Antagonist ◽  
Synaptic Excitation ◽  
Spinal Neurones

ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes

2002 ◽  
Vol 283 (2) ◽  
pp. C569-C578 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Atp Release ◽  
Anion Channel ◽  
P2y Receptors ◽  
Cell Swelling ◽  
Channel Blockers ◽  
Medium Osmolarity ◽  
Subsequent Activation

Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the brain ATP is released by both neurons and astrocytes and participates in intercellular communication. We explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 μM) activated a small EAA release in 70–80% of the cultures tested. In both moderately (5% reduction of medium osmolarity) and substantially (35% reduction of medium osmolarity) swollen astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in nonswollen and moderately swollen cells was eliminated by a 5–10% increase in medium osmolarity or by anion channel blockers but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bidirectional neuron-astrocyte communication in vivo.

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