Effects of a New Excitotoxic Amino Acid, Dysiherbaine, on Cultured Muller Cells.

摘要

PURPOSE: To determine the pharmacological response when dysiherbaine acts on cultured Muller 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 Muller 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 &mgr;M-2.5 mM) to Muller 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 Muller 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.