Disease relevance of Homoquinolinate

• Dextromethorphan at 500 nmol/embryo/d killed more than half the embryos and induced congenital defects in about one-eighth of the survivors; dextromethorphan was also highly lethal at 50 nmol/embryo/d. Glutamate site NMDA receptor agonists (NMDA and homoquinolinic acid) displayed weak toxicity relative to their known NMDA receptor potency [1].

High impact information on Homoquinolinate

• In contrast to an autoradiographical study, these radioligand binding and electrophysiological experiments suggest that homoquinolinate is not highly selective for NR2B-containing receptors [2].
• N-Methyl-D-aspartate receptor subtype-selectivity of homoquinolinate: an electrophysiological and radioligand binding study using both native and recombinant receptors [2].
• We found that chronic morphine treatment did not alter the affinity for NMDA receptor agonists such as glutamate, homoquinolinic acid, and NMDA, but decreased the affinity of glycine, the allosteric NMDA receptor coagonist, from 2.24 +/- 0.15 microM to 5.1 +/- 1.45 microM [3].
• In both layers, bath application of the NR2A/B subunit-selective agonist, homoquinolinic acid (HQA), resulted in a marked facilitation of mEPSC frequency [4].
• The relative efficacies of quinolinic acid and homoquinolinic acid were evaluated by comparing the maximal responses induced by these agonists with those induced by NMDA and glutamate in the same oocytes [5].

Associations of Homoquinolinate with other chemical compounds

• Since homoquinolinic acid is a rigid analogue of glutamic acid, but causes excitation by acting apparently on the NMDA receptor, the results are consistent with the suggestion that activation of the NMDA receptor may require the carboxyl groups to be held in a relatively extended configuration [6].
• Molecular dynamics simulations and site-directed mutagenesis demonstrate that the partial agonist homoquinolinate interacts differently with binding pocket residues than glutamate [7].

Gene context of Homoquinolinate

• Chronic morphine did not alter the affinity for NMDAR agonists glutamate, homoquinolinate, or NMDA, but decreased the affinity of the coagonist glycine [8].
• Certain compounds which discriminate between medial thalamic and cerebellar (presumed to contain NR2C subunits) receptors (e.g., homoquinolinate, D-CPPene) did not show a similar selectivity for NR1a/NR2D receptors relative to NR1/NR2C receptors [9].

References