TY - JOUR
T1 - Pharmacological characterization of metabotropic glutamate receptors in cultured cerebellar granule cells
AU - Aronica, E.
AU - Nicoletti, F.
AU - Condorelli, D. F.
AU - Balázs, R.
PY - 1993
Y1 - 1993
N2 - A detailed pharmacological characterization of metabotropic glutamate receptors (mGluR) was performed in primary cultures of cerebellar granule cells at 6 days in vitro (DIV). The rank order of agonists induced polyphosphoinositide (PPI) hydrolysis (after correcting for the ionotropic component in the response) was as follows: in terms of efficiency, Glu > quisqualate (quis) = ibotenate (ibo) > (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) > beta-methyl-amino-L-alanine (BMAA) and in terms of potency, quis > ACPD > Glu > ibo = BMAA. Ionotropic excitatory amino acid (EAA) receptor agonists, such as alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) were relatively inactive (in the presence of Mg2+). Quis and ACPD-induced PPI hydrolysis was unaffected by ionotropic Glu receptor antagonists, but was inhibited, in part by L-2-amino-3-phosphonopropionate (AP3). In contrast, Glu-or ibo- induced PPI hydrolysis was reduced, in part, by both AP3 and NMDA receptor antagonists. Characteristic interactions involving different transmitter receptors were noted. PPI hydrolysis evoked by quis and 1S,3R-ACPD was not additive. In contrast, PPI hydrolysis stimulated by quis/ACPD and carbamylcholine was additive (indicating different receptors/transduction pathways). In the presence of Mg2+, the metabotropic response to quis/AMPA and NMDA was synergistic (this being consistent with AMPA receptor-induced depolarization activating NMDA receptor). On the other hand, in Mg(2+)-free buffer the effects of quis and NMDA, at concentrations causing maximal PPI hydrolysis, were additive (indicating that PPI hydrolysis was effected by two different mechanisms).(ABSTRACT TRUNCATED AT 250 WORDS)
AB - A detailed pharmacological characterization of metabotropic glutamate receptors (mGluR) was performed in primary cultures of cerebellar granule cells at 6 days in vitro (DIV). The rank order of agonists induced polyphosphoinositide (PPI) hydrolysis (after correcting for the ionotropic component in the response) was as follows: in terms of efficiency, Glu > quisqualate (quis) = ibotenate (ibo) > (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) > beta-methyl-amino-L-alanine (BMAA) and in terms of potency, quis > ACPD > Glu > ibo = BMAA. Ionotropic excitatory amino acid (EAA) receptor agonists, such as alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) were relatively inactive (in the presence of Mg2+). Quis and ACPD-induced PPI hydrolysis was unaffected by ionotropic Glu receptor antagonists, but was inhibited, in part by L-2-amino-3-phosphonopropionate (AP3). In contrast, Glu-or ibo- induced PPI hydrolysis was reduced, in part, by both AP3 and NMDA receptor antagonists. Characteristic interactions involving different transmitter receptors were noted. PPI hydrolysis evoked by quis and 1S,3R-ACPD was not additive. In contrast, PPI hydrolysis stimulated by quis/ACPD and carbamylcholine was additive (indicating different receptors/transduction pathways). In the presence of Mg2+, the metabotropic response to quis/AMPA and NMDA was synergistic (this being consistent with AMPA receptor-induced depolarization activating NMDA receptor). On the other hand, in Mg(2+)-free buffer the effects of quis and NMDA, at concentrations causing maximal PPI hydrolysis, were additive (indicating that PPI hydrolysis was effected by two different mechanisms).(ABSTRACT TRUNCATED AT 250 WORDS)
U2 - https://doi.org/10.1007/BF00966938
DO - https://doi.org/10.1007/BF00966938
M3 - Article
C2 - 8097299
SN - 0364-3190
VL - 18
SP - 605
EP - 612
JO - Neurochemical research
JF - Neurochemical research
IS - 5
ER -