Effects of a new excitotoxic amino acid, dysiherbaine, on cultured Müller cells.
OBJECTIVE
To determine the pharmacological response when dysiherbaine acts on cultured Müller cells, considering the glutamate receptor functions. Dysiherbaine is a new excitotoxic amino acid, which was recently isolated from the liquid extract of a certain sponge.


METHODS
Retinas of adult rabbits were used to culture the Müller cells. Intracellular calcium ion concentration ([Ca(2+)](i)) analysis was done by fluorophotometry with the calcium indicator, acetoxymethyl ester fura-2 (Fura-2 AM).


RESULTS
A transient increase of [Ca(2+)](i) was observed following the administration of dysiherbaine (2.5 microM-2.5 mM) to Müller cells, but no [Ca(2+)](i) increase was observed in the extracellular calcium-free solution. This increase was blocked by the non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX). A dysiherbaine-induced increase in [Ca(2+)](i) following preincubation of the NMDA glutamate receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dyhydro-5H-dibenzo [a,d] cyclohepten-5, 10-imine hydrogen maleate (MK 801) was seen in the same number of Müller cells with and without the antagonist.


CONCLUSIONS
Dysiherbaine appears to act primarily as a non-NMDA glutamate receptor agonist, having a secondary action as a NMDA glutamate receptor agonist.
Minei
Risako
R
Department of Ophthalmology, Kitasato University, School of Medicine, Sagimihara, Kanagawa, Japan
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015590:Fluorophotometry; D016257:Fura-2 / Q000031:analogs & derivatives* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D012160:Retina / Q000166:cytology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C121741:dysiherbaine; C049925:fura-2-am; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000409:Alanine; D002118:Calcium; D016257:Fura-2