TY - JOUR
T1 - The depolarization-induced outflow of d-[3H]aspartate from rat brain slices is modulated by metabotropic glutamate receptors
AU - Lombardi, Grazia
AU - Pellegrini-Giampietro, Domenico E.
AU - Leonardi, Patrizia
AU - Cherici, Giovanna
AU - Pellicciari, Roberto
AU - Moroni, Flavio
N1 - Funding Information:
Acknowled#ements--Supported by the National Research Council (C.N.R.), the University of Florence and the European Economic Community Biomed 1 project No. BMH 1-CT93-1033. The technical assistance of Dr A. Cozzi is gratefully acknowledged.
PY - 1994/6
Y1 - 1994/6
N2 - Rat brain slices were used to study the effects of different metabotropic glutamate receptor ligands on (i) the depolarization (30 mM KCl)-induced outflow of previously taken up d-[3H]aspartate; (ii) the inhibition of forskolin (30 μM)-induced cyclic AMP accumulation; and (iii) the hydrolysis of phosphoinositides. In addition, the localization of mRNAs coding for different metabotropic glutamate receptor subtypes was detected using in situ hybridization. (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (30-300 μM), a non selective metabotropic glutamate receptor agonist, significantly increased the KCl-induced output of radioactivity from cortical slices, whereas it inhibited the output from striatal slices. Conversely, (1S,3S,4S)-carboxycyclopropylglycine (0.1-1 μM), a relatively selective agonist of the mGluR2 metabotropic glutamate receptor subtype, had an inhibitory effect on the output of d-[3H]aspartate from both cortical and striatal slices and proved to be the most potent metabotropic glutamate receptor agonist in inhibiting cyclic AMP accumulation, but not in stimulating phosphoinositide hydrolysis. Since 2-amino-4-phosphonobutyrate (a mGluR4, mGluR6 and mGluR7 agonist) was not active in any of the assays tested, we hypothesized that the mGluR2 subtype could be involved in these events. Accordingly, mGluR2 mRNA expression was abundant in cortical neurons projecting to the striatum. Our experiments suggest that the stimulation of metabotropic glutamate receptors may either decrease or increase transmitter release depending on the subtype that prevails in the region under study.
AB - Rat brain slices were used to study the effects of different metabotropic glutamate receptor ligands on (i) the depolarization (30 mM KCl)-induced outflow of previously taken up d-[3H]aspartate; (ii) the inhibition of forskolin (30 μM)-induced cyclic AMP accumulation; and (iii) the hydrolysis of phosphoinositides. In addition, the localization of mRNAs coding for different metabotropic glutamate receptor subtypes was detected using in situ hybridization. (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (30-300 μM), a non selective metabotropic glutamate receptor agonist, significantly increased the KCl-induced output of radioactivity from cortical slices, whereas it inhibited the output from striatal slices. Conversely, (1S,3S,4S)-carboxycyclopropylglycine (0.1-1 μM), a relatively selective agonist of the mGluR2 metabotropic glutamate receptor subtype, had an inhibitory effect on the output of d-[3H]aspartate from both cortical and striatal slices and proved to be the most potent metabotropic glutamate receptor agonist in inhibiting cyclic AMP accumulation, but not in stimulating phosphoinositide hydrolysis. Since 2-amino-4-phosphonobutyrate (a mGluR4, mGluR6 and mGluR7 agonist) was not active in any of the assays tested, we hypothesized that the mGluR2 subtype could be involved in these events. Accordingly, mGluR2 mRNA expression was abundant in cortical neurons projecting to the striatum. Our experiments suggest that the stimulation of metabotropic glutamate receptors may either decrease or increase transmitter release depending on the subtype that prevails in the region under study.
UR - http://www.scopus.com/inward/record.url?scp=0028225220&partnerID=8YFLogxK
U2 - 10.1016/0197-0186(94)90003-5
DO - 10.1016/0197-0186(94)90003-5
M3 - Article
SN - 0197-0186
VL - 24
SP - 525
EP - 532
JO - Neurochemistry International
JF - Neurochemistry International
IS - 6
ER -