A MARKED INCREASE IN INTRACELLULAR CA2+ CONCENTRATION INDUCED BY ACROMELIC ACID IN CULTURED RAT SPINAL NEURONS

Acromelic acid, a kainate derivative of natural origin, markedly incre ased intracellular Ca2+ concentration ([Ca2+](i) in cultured rat spina l neurons in a concentration dependent manner; the half effective conc entration (EC(50)) was 1.3 mu M. Acromelic acid was more potent in inc reasing [Ca2+](i), than any other glutamate receptor agonists tested, and the rank order of the activity was as follows: acromelic acid > lp ha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) > kainate > N-methyl-D-aspartate(NMDA) > L-glutamate. Acromelic acid did not inc rease the [Ca2+](i) in a Ca2+-free medium. 3-Dihydroxy-9-nitro-7-sulfa moylbenzo(F)quinoxaline (NBQX) completely inhibited the [Ca2+](i) incr ease induced by acromelic acid. These results suggest that the [Ca2+]( i) increase was not through Ca2+ mobilization from intracellular store s but due to Ca2+ influx mediated by the activation of non-NMDA recept ors. Acromelic acid increased the [Ca2+](i) in rat hippocampal neurons as well; however, the EC(50) (6 mu M) was considerably higher than th at in spinal neurons. The marked increase of [Ca2+](i) in cultured spi nal neurons would explain, at least in part, the earlier findings that systemic administration of acromelic acid causes selective degenerati on confined to lower spinal interneurons.