Biomedical subjects

H Monyer

Publications and source records attributed to H Monyer.

58 records · Page 4Linked to original sources

PubMed1988

Hypoxic neuronal injury in vitro depends on extracellular glutamine.

Hypoxic neuronal injury (HNI) in cortical cell cultures was enhanced in a concentration-dependent fashion by the presence of 500 microM to 2 mM (EC50 about 500 microM) glutamine in the medium, concentrations approximating those normally present in cerebrospinal fluid (CSF). Regardless of the glutamine concentration, glutamate receptor antagonists 2-amino-5-phosphonovalerate or dextrorphan could substantially reduce HNI. Thus, the availability of extracellular glutamine could be a determinant of hypoxic neuronal injury in vivo, most likely reflecting its importance in the synthesis of the neurotransmitter excitotoxins glutamate and aspartate.

Anaerobiosis↗

PubMed1988

Tetrahydroaminoacridine selectively attenuates NMDA receptor-mediated neurotoxicity.

Addition of the acetylcholinesterase inhibitor 1,2,3,4-tetra-9-hydroaminoacridine (THA) at 1-3 mM markedly reduced the neuronal cell loss that otherwise followed brief exposure of murine cortical cell cultures to 500 microM N-methyl-D-aspartate (NMDA). This novel antagonism was selective for NMDA receptor-mediated toxicity, as it extended to glutamate toxicity but not to quisqualate toxicity, and was THA concentration-dependent between 100 microM and 3 mM, with IC50 approximately 500 microM. The antagonism was probably not due to enhancement of endogenous cholinergic action, as it was not mimicked by acetylcholine, carbachol, or bethanechol; rather, it likely reflected a recently described interaction of THA with the phencyclidine receptor. Exploration of structural specificity revealed some partial neuron-protection with high concentrations of other cholinesterase inhibitors--physostigmine, neostigmine, and edrophonium, but not the structurally related potassium channel blocker, 4-aminopyridine. Further examination of correlations between THA-like structure, and neuron-protective activity, may provide useful insights in the development of new antagonists of NMDA receptor-mediated neurotoxicity.

Aminoacridines↗

PubMed1988

Adenosine reduces cortical neuronal injury induced by oxygen or glucose deprivation in vitro.

The endogenous neuromodulatory purine, adenosine, substantially attenuated neuronal degeneration when added to dissociated cortical cell cultures acutely deprived of either oxygen or glucose. The protective effect of adenosine, was concentration-dependent between 30 and 1000 microM (EC50 about 100 microM), and could be mimicked by the stable adenosine analogue N6-cyclohexyladenosine (10 microM). Unlike postsynaptic glutamate receptor antagonists, which also block these forms of neuronal injury, adenosine did not alter the neurotoxicity of exogenously applied glutamate.

Adenosine↗

PubMed1988

Morphinans attenuate cortical neuronal injury induced by glucose deprivation in vitro.

The non-narcotic dextrorotatory morphinan, dextrorphan, as well as its levorotatory opioid enantiomer, levorphanol, and its O-methyl derivative, dextromethorphan, have recently been shown to antagonize N-methyl-D-aspartate receptor-mediated neurotoxicity. Consistent with in vivo data suggesting that this neurotoxicity contributes to the neuronal damage associated with hypoglycemia, micromolar concentrations of these morphinans markedly attenuated the injury of cultured mouse cortical neurons produced by acute glucose deprivation. These observations lend specific support to the possibility that morphinan compounds may prove to have clinical therapeutic utility in hypoglycemic encephalopathy.

Animals↗