Effects of a new excitotoxic amino acid, dysiherbaine, on cultured Muller cells

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 ([Ca2+](i)) analysis was done by fluorophotometry with the calcium indicator, acetoxymethyl ester fura-2 (Fura-2 AM). Results: A transient increase of [Ca2+](i) was observed following the administration of dysiherbaine (2.5 muM-2.5 mM) to Muller cells. but no [Ca2+](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 [Ca2+](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 bells 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. (C) 2002 Japanese Ophthalmological Society.