Modulation of NMDA-induced cytosolic calcium levels by ACPC in cultured cerebellar granule cells.
The effect of 1-aminocyclopropanecarboxylic acid (ACPC) on the potentiation by glycine of N-methyl-D-aspartate (NMDA)-evoked increases in intracellular free calcium concentration [Ca2+]i was examined in cultured rat cerebellar granule cells. NMDA (50 microM) produced a rapid and sustained increase in [Ca2+]i from 72 +/- 3 to 205 +/- 18 nM. Addition of exogenous glycine potentiated (EC50 -2 microM) the effects of NMDA, increasing [Ca2+]i to an Emax of 323 +/- 5 nM. ACPC increased the EC50 of glycine from 2 microM (no ACPC) to 17 microM (400 microM ACPC). Concomitant with reduced potency of glycine, ACPC also inhibited the Emax of glycine to enhance NMDA-evoked cytosolic free calcium to values (224 +/- 1 nM) approaching those observed in the nominal absence of glycine. These results show that ACPC, a compound previously reported to prevent excitotoxic cell death, inhibits the glycine-induced increase of Ca2+ entry through NMDA receptors in cerebellar granule cells.
Unitat de Neurobiologia, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, CSIC, Spain.
F X
FX
Sureda
E
E
Viu
A
A
Zapata
J L
JL
Capdevila
A
A
Camins
E
E
Escubedo
J
J
Camarasa
R
R
Trullas
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects*; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D003521:Cyclopropanes; C015766:cyclopropanecarboxylic acid; D016202:N-Methylaspartate; D002118:Calcium; D005998:Glycine