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 increased intracellular Ca2+ concentration ([Ca2+]i) in cultured rat spinal neurons in a concentration dependent manner; the half effective concentration (EC50) was 1.3 microM. Acromelic acid was more potent in increasing [Ca2+]i than any other glutamate receptor agonists tested, and the rank order of the activity was as follows: acromelic acid > alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) > kainate > N-methyl-D-aspartate (NMDA) > L-glutamate. Acromelic acid did not increase the [Ca2+]i in a Ca(2+-)free medium. 2,3-Dihydroxy-9-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX) completely inhibited the [Ca2+]i increase induced by acromelic acid. These results suggest that the [Ca2+]i increase was not through Ca2+ mobilization from intracellular stores but due to Ca2+ influx mediated by the activation of non-NMDA receptors. Acromelic acid increased the [Ca2+]i in rat hippocampal neurons as well; however, the EC50 (6 microM) was considerably higher than that in spinal neurons. The marked increase of [Ca2+]i in cultured spinal neurons would explain, at least in part, the earlier findings that systemic administration of acromelic acid causes selective degeneration confined to lower spinal interneurons.
Department of Physiology, Ehime University, School of Medicine, Japan.
T
T
Ogata
Y
Y
Nakamura
K
K
Tsuji
T
T
Shibata
K
K
Kataoka
M
M
Ishida
H
H
Shinozaki
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
D018690:Excitatory Amino Acid Agonists; D017470:Receptors, Glutamate; C051743:acromelic acid A; D007608:Kainic Acid; D002118:Calcium