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NMDA and Non‐NMDA Ionotropic Glutamate Receptors Modulate Striatal Acetylcholine Release via Pre‐ and Postsynaptic Mechanisms
Author(s) -
Morari M.,
Sbrenna S.,
Marti M.,
Caliari F.,
Bianchi C.,
Beani L.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71052006.x
Subject(s) - ampa receptor , nmda receptor , cnqx , dizocilpine , chemistry , acetylcholine , ionotropic effect , kainate receptor , glutamate receptor , pharmacology , biology , biochemistry , receptor
The effects of NMDA and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) on endogenous acetylcholine release from rat striatal slices and synaptosomes were investigated. Both agonists (1–300 µ M ) facilitated acetylcholine release from slices in a dose‐dependent manner. NMDA (100–300 µ M ) and AMPA (30–300 µ M ), however, subsequently inhibited acetylcholine release. NMDA (100 µ M )‐induced facilitation was antagonized by 3‐(2‐carboxypiperazin‐4‐yl)propyl‐1‐phosphonic acid (CPP) and dizocilpine (both 1–10 µ M ), whereas the 10 µ M AMPA effect was antagonized by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; 1–30 µ M ). NMDA (100 µ M )‐induced inhibition was counteracted by CPP, but not dizocilpine, and by the nitric oxide synthase inhibitor l ‐nitroarginine (1–100 µ M ). Tetrodotoxin (0.5 µ M ) prevented the facilitatory effect of 3 µ M NMDA and AMPA, but left unchanged that of 30 µ M NMDA and 100 µ M AMPA. Acetylcholine release from synaptosomes was stimulated by KCI (7.5–100 m M ) in a dose‐dependent manner. NMDA and AMPA maximally potentiated the 20 m M KCl effect at 1 µ M and 0.01 µ M , but were ineffective at 100 µ M and 10 µ M , respectively. Inhibition of acetylcholine release was never found in synaptosomes. The effects of 1 µ M NMDA and 0.01 µ M AMPA were antagonized by CPP (0.0001–1 µ M ) or dizocilpine (0.0001–10 µ M ) and by CNQX (0.001–1 µ M ), respectively. These data suggest that glutamatergic control of striatal acetylcholine release is mediated via both pre‐ and post‐synaptic NMDA and non‐NMDA ionotropic receptors.