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VOL. 76 (1), 3-22, 2010 CROSS-TALK BETWEEN GLUTAMATE AND NUCLEOTIDE...

3.3. Both NMDA and non-NMDA ionotropic glutamate
3.3. receptors reduce the ATP-induced intracellular
3.3. calcium increase

L-Glu acts as a mixed agonist for all classes of ionotropic

glutamate receptor. To investigate the glutamate receptor involved

in the L-Glu inhibitory effects on nucleotide receptors, we tested

the actions of AMPA, NMDA and non-NMDA receptors agonists

respectively, on ATP-induced responses. NMDA (100 µM) applied
immediately before ATP (200 µM) increased [Ca2+]i by itself (214 ±
20 nM; n = 70 neurons) and significantly suppressed the [Ca2+]i
increase induced by ATP (Figure 4A). The pooled average depression

compared with the control ATP-induced response were 70 ± 11%

(p < 0.01, n = 70 neurons) and 75 ± 2% (p < 0.05, n = 70 neurons)

at 0 and 5 min, respectively. Similar results were observed when

AMPA (100 µM) was assayed (Figure 4B). Thus, AMPA was also
able to increase [Ca2+]i by itself (254 ± 29 nM; n = 57 neurons) and
to depress ATP-induced currents in a similar extent at both times

studied (77 ± 2%, p < 0.001, n = 57 neurons at 0 min and 77 ± 4%,

p < 0.001, n = 57 neurons at 5 min).

3.4. Group I mGluR activation decrease ATP-induced
3.4. responses

Previous works have shown the presence of functional Group I
mGluR in cerebellar granule neurons (3) where it is probably that they
are involved in synaptic plasticity (22). The possible participation of
Group I mGluR in the L-Glu inhibitory effects on nucleotide receptors
was studied using 100 µM DHPG as specific agonist (23). As it is
shown in Figure 4C, DHPG (100 µM) increased [Ca2+]i (133 ± 58 nM)
and also significantly decreased ATP-induced responses to a value that
was 52 ± 5% of their initial value (p < 0.001, n = 50 neurons). This loss
of responsiveness remained 5 min after DHPG (100 µM) application
(60 ± 5%, p < 0.001, n = 50 neurons).

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