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Analogues of homoibotenic acid show potent and selective activity following sensitisation by quisqualic acid
Ist Teil von
European journal of pharmacology, 2004-03, Vol.488 (1), p.101-109
Ort / Verlag
Amsterdam: Elsevier B.V
Erscheinungsjahr
2004
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Quisqualic acid induces sensitisation of neurones to depolarisation by analogues of 2-amino-4-phosphonobutyric acid (AP4), phenylglycine, and homoibotenic acid (HIBO). Thus, after administration of quisqualate these analogues become active at concentrations at which they are otherwise inactive. The mechanisms behind quisqualate-induced sensitisation are poorly understood and have not previously been quantified properly. In this study, we have tested the activity of a number of 4-alkyl- and 4-aryl-substituted analogues of HIBO as regards quisqualate-sensitisation, and present a method for quantifying the sensitisation induced by quisqualate at cortical neurones. These analogues are generally more potent and selective than (
S)-AP4 or its homologue (
S)-AP5 following quisqualate-sensitisation. Furthermore, we found a statistically significant correlation between the ligands' ability to inhibit CaCl
2-dependent (
S)-[
3H]glutamate uptake into rat cortical synaptosomes, and their potency following quisqualate-induced depolarisation. This demonstrates the involvement of a transport system in the mechanism underlying the quisqualate-effect.