TY - JOUR
T1 - Pertussis toxin inhibits signal transduction at a specific metabolotropic glutamate receptor in primary cultures of cerebellar granule cells
AU - Nicoletti, F.
AU - Wroblewski, J. T.
AU - Fadda, E.
AU - Costa, E.
PY - 1988
Y1 - 1988
N2 - In primary cultures of cerebellar granule cells, glutamate receptors have been classified into metabolotroplc (GP1 and GP2) and ionotroplc (GC1 and GC2). The GP1 and GC1 receptors are negatively modulated by magnesium and noncompetitively inhibited by phencyclidine; GP2 and GC2 receptors are insensitive to inhibition by magnesium and phencyclidine (Costa, Fadda, Kozikowski, Nicoletti and Wroblewski, 1988). Exposure of cultured cerebellar granule cells to pertussis toxin (PTX, 1 μg/ml for 14-16 hr) reduced the stimulation of the hydrolysis of inositol phospholipids (PI) by the GP2 receptor agonists, glutamate and quisqualate in the presence of magnesium, but did not inhibit the stimulation of the hydrolysis of PI by GP1, receptor agonists. The stimulation of the hydrolysis of PI by the muscarinic cholinergic receptor agonist, carbamylcholine, remained unchanged after pretreatment with pertussis toxin. In membranes prepared from cerebellar granule cells in primary culture, the addition of guanosine 5′-0-(3-thiotriphosphate) (GTP-γ-s), a nonhydrolyzable analogue of GTP, enhanced the hydrolysis of PI and reduced the Bmax of quisqualate-displaceable binding of [3H]glutamate. These results indicate that, in primary cultures of cerebellar granule cells, a specific class of metabolotroplc glutamate receptors (the GP2 receptor) is coupled with the hydrolysis of PI through a pertussis toxin-sensitive GTP-binding protein.
AB - In primary cultures of cerebellar granule cells, glutamate receptors have been classified into metabolotroplc (GP1 and GP2) and ionotroplc (GC1 and GC2). The GP1 and GC1 receptors are negatively modulated by magnesium and noncompetitively inhibited by phencyclidine; GP2 and GC2 receptors are insensitive to inhibition by magnesium and phencyclidine (Costa, Fadda, Kozikowski, Nicoletti and Wroblewski, 1988). Exposure of cultured cerebellar granule cells to pertussis toxin (PTX, 1 μg/ml for 14-16 hr) reduced the stimulation of the hydrolysis of inositol phospholipids (PI) by the GP2 receptor agonists, glutamate and quisqualate in the presence of magnesium, but did not inhibit the stimulation of the hydrolysis of PI by GP1, receptor agonists. The stimulation of the hydrolysis of PI by the muscarinic cholinergic receptor agonist, carbamylcholine, remained unchanged after pretreatment with pertussis toxin. In membranes prepared from cerebellar granule cells in primary culture, the addition of guanosine 5′-0-(3-thiotriphosphate) (GTP-γ-s), a nonhydrolyzable analogue of GTP, enhanced the hydrolysis of PI and reduced the Bmax of quisqualate-displaceable binding of [3H]glutamate. These results indicate that, in primary cultures of cerebellar granule cells, a specific class of metabolotroplc glutamate receptors (the GP2 receptor) is coupled with the hydrolysis of PI through a pertussis toxin-sensitive GTP-binding protein.
KW - G protein
KW - glutamate receptors
KW - pertussis toxin
KW - PI hydrolysis
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U2 - 10.1016/0028-3908(88)90174-8
DO - 10.1016/0028-3908(88)90174-8
M3 - Article
C2 - 2843781
AN - SCOPUS:0023938146
VL - 27
SP - 551
EP - 556
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 6
ER -